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Yawning is considered a brainstem regulated behavior which is associated with changes in arousal and activity levels. Yawning and stretching are dopamine (DA) mediated behaviors and pharmacological studies indicate that these behaviors are associated with increased DA release coupled with stimulation of postsynaptic DA-D2 receptors. Despite their relation to the dopaminergic system, yawning and stretching are poorly documented in untreated or treated patients with Parkinson's disease (PD). A 49 year old fully medicated female patient with juvenile onset PD is presented in whom recurrent episodes of yawning and stretching developed during transcranial administration of AC pulsed electromagnetic fields (EM Fs) of picotesla flux density. These episodes have not been observed previously in this or other patients during treatment with levodopa or DA receptor agonists or in unmedicated PD patients during treatment with AC pulsed EMFs. It is suggested that yawning and stretching behavior resulted in this patient from a synergistic interaction between EMFs and DA derived from levodopa supplementation with EMFs possibly facilitating the release of DA and simultaneously activating postsynaptic DA-D2 receptors in the nigrostriatal dopaminergic pathways. In addition, it is postulated that the release of ACTH/MSH peptides from peptidergic neurons in the brain upon stimulation of the DA-D2 receptors reinforced the yawning and stretching behavior.

Sexual dysfunction is common in patients with Parkinson's disease (PD) since brain dopaminergic mechanisms are involved in the regulation of sexual behavior. Activation of dopamine D2 receptor sites, with resultant release of oxytocin from the paraventricular nucleus (PVN) of the hypothalamus, induces sexual arousal and erectile responses in experimental animals and humans. In Parkinsonian patients subcutaneous administration of apomorphine, a dopamine D2 receptor agonist, induces sexual arousal and penile erections. It has been suggested that the therapeutic efficacy of transcranial administration of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density in PD involves the activation of dopamine D2 receptor sites which are the principal site of action of dopaminergic pharmacotherapy in PD. Here, 1 report 2 elderly male PD patients who experienced sexual dysfunction which was recalcitrant to treatment with anti Parkinsonian agents including selegiline, levodopa and tolcapone. However, brief transcranial administrations of AC pulsed EMFs in the picotesla flux density induced in these patients sexual arousal and spontaneous nocturnal erections. These findings support the notion that central activation of dopamine D2 receptor sites is associated with the therapeutic efficacy of AC pulsed EMFs in PD. In addition, since the right hemisphere is dominant for sexual activity, partly because of a dopaminergic bias of this hemisphere, these findings suggest that right hemispheric activation in response to administration of AC pulsed EMFs was associated in these patient with improved sexual functions.

The Draw-a-Bicycle Test is employed in neuropsychological testing of cognitive skills since the bicycle design is widely known and also because of its complex structure. The Draw-a-Bicycle Test has been administered routinely to patients with Parkinson's disease (PD) and other neurodegenerative disorders to evaluate the effect of transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density on visuoconstructional skills. A seminal observation is reported in 5 medicated PD patients who demonstrated reversal of spontaneous drawing direction of the bicycle after they received a series of transcranial treatments with AC pulsed EMFs. In 3 patients reversal of the bicycle drawing direction was observed shortly after the administration of pulsed EMFs while in 2 patients these changes were observed within a time lag ranging from several weeks to months. All patients also demonstrated a dramatic clinical response to the administration of EMFs. These findings are intriguing because changes in drawing direction do not occur spontaneously in normal individuals as a result of relateralization of cognitive functions. This report suggests that administration of AC pulsed EMFs may induce in some PD patients changes in hemispheric dominance during processing of a visuoconstructional task and that these changes may be predictive of a particularly favourable response to AC pulsed EMFs therapy.

Cessation of dream recall has been reported in numerous neurological disorders including multiple sclerosis (MS). Two women MS patients are presented in whom transcranial treatment with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density restored dream recall and 4 to 5 months later induced vivid colored dreams. The experience of colored dreams coincided with a period of distinctive improvement in visual acuity, color vision, and depth perception and in one patient with normalization of the visual evoked potential latencies. Dreams associated with REM sleep are reported to be vivid, colorful and lengthy and administration of melatonin facilitates REM sleep and increases its duration in humans. Additionally, melatonin administered at night induces vivid colored dreams in normal subjects and narcoleptic patients. Therefore, since melatonin secretion is sensitive to the effects of pulsed EMFs these findings suggest that the experience of colored dreams in these patients was probably related...

Seasonal variation in symptoms of multiple sclerosis (MS) has been well documented in the literature and points to the influence of environmental factors on the pathogenesis of the disease. The majority of these studies indicate an increased rate of exacerbation during the spring and/or autumn both of which are associated with desynchronization of circadian pineal melatonin secretion with nadirs in plasma melatonin levels. Three MS patients who experienced annually recurrent and incapacitating seasonal exacerbations of existing symptoms are presented. The first patient, a 49 year old woman, developed over the past 6 years recurrent exacerbations of symptoms in the spring which lasted for about a month. The second patient, a 53 year old woman, experienced over the past 7 years recurrent exacerbations of symptoms in the autumn which lasted through January of the following year. The third patient, a 42 year old woman, experienced recurrent exacerbations of symptoms in the spring and autumn over the past 15 y...

Visual evoked response (VER) studies have been utilized as supportive information for the diagnosis of multiple sclerosis (MS) and may be useful in objectively monitoring the effects of various therapeutic modalities. Delayed latency of the VER, which reflects slowed impulse transmission in the optic pathways, is the most characteristic abnormality associated with the disease. Brief transcranial applications of AC pulsed electromagnetic fields (EMFs) in the picotesla flux density are efficacious in the symptomatic treatment of MS and may also reestablish impulse transmission in the optic pathways. A 36 year old man developed an attack of right sided optic neuritis at the age of 30. On presentation he had blurring of vision with reduced acuity on the right and fundoscopic examination revealed pallor of the optic disc. A checkerboard pattern reversal VER showed a delayed latency to right eye stimulation (P100 = 132 ms; normal range: 95-115 ms). After he received two successive applications of AC pulsed EMFs of 7.5 picotesla flux density each of 20 minutes duration administered transcranially, there was a dramatic improvement in vision and the VER latency reverted to normal (P100= 107 ms). The rapid improvement in vision coupled with the normalization of the VER latency despite the presence of optic atrophy, which reflects chronic demyelination of the optic nerve, cannot be explained on the basis of partial or full reformation of myelin. It is proposed that in MS synaptic neurotransmitter deficiency is associated with the visual impairment and delayed VER latency following optic neuritis and that the recovery of the VER latency by treatment with pulsed EMFs is related to enhancement of synaptic neurotransmitter functions in the retina and central optic pathways. Recovery of the VER latency in MS patients may have important implications with respect to the treatment of visual impairment and prevention of visual loss. Specifically, repeated pulsed applications of EMFs may maintain impulse transmission in the optic nerve and thus potentially sustain its viability.

Cognitive deficits are common among patients with multiple sclerosis (MS). The pathogenetic mechanisms underlying the cognitive impairment in MS are unknown and there is presently no effective therapeutic modality which has shown efficacy in improving cognitive deficits in MS. A 53 year old college professor with a long history of secondary progressive MS experienced, over the preceding year, noticeable deterioration in cognitive functions with difficulties in short and long term memory, word finding in spontaneous speech, attention and concentration span. Unable to pursue his academic activities, he was considering early retirement. Mental examination disclosed features of subcortical and cortical dementia involving frontal lobe, left hemispheric and right hemispheric dysfunction. Almost immediately following the extracerebral application of AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla intensity and a 4-Hz sinusoidal wave, the patient experienced a heightend sense of well being, which he defined as enhancement of cognitive functions with a feeling "like a cloud lifted off my head." He reported heightend clarity of thinking and during the application of EMFs he felt that words were formed faster and he experienced no difficulty finding the appropriate words. His speech was stronger and well modulated and he felt "energized" with resolution of his fatigue. There was improvement in manual dexterity and handwriting and testing of constructional praxis demonstrated improvement in visuospatial, visuoperceptive and visuomotor functions. It is suggested that some of the cognitive deficits associated with MS, which are caused by synaptic disruption of neurotransmitter functions, may be reversed through pulsed applications of picotesla range EMFs.

Absent or markedly reduced REM sleep with cessation of dream recall has been documented in numerous neurological disorders associated with subcortical dementia including Parkinson's disease, progressive supranuclear palsy and Huntington's chorea. This report concerns a 69 year old Parkinsonian patient who experienced complete cessation of dreaming since the onset of motor disability 13 years ago. Long term treatment with levodopa and dopamine (DA) receptor agonists (bromocriptine and pergolide mesylate) did not affect dream recall. However, dreaming was restored after the patient received three treatment sessions with AC pulsed picotesla range electromagnetic fields (EMFs) applied extracranially over three successive days. Six months later, during which time the patient received 3 additional treatment sessions with EMFs, he reported dreaming vividly with intense colored visual imagery almost every night with some of the dreams having sexual content. In addition, he began to experience hypnagogic imagery prior to the onset of sleep. Cessation of dream recall has been associated with right hemispheric dysfunction and its restoration by treatment with EMFs points to right hemispheric activation, which is supported by improvement in this patient's visual memory known to be subserved by the right temporal lobe. Moreover, since DA neurons activate REM sleep mechanisms and facilitate dream recall, it appears that application of EMFs enhanced DA activity in the mesolimbic system which has been implicated in dream recall. Also, since administration of pineal melatonin has been reported to induce vivid dreams with intense colored visual imagery in normal subjects and narcoleptic patients, it is suggested that enhanced nocturnal melatonin secretion was associated with restoration of dream recall in this patient. These findings demonstrate that unlike chronic levodopa therapy, intermittent pulsed applications of AC picotesla EMFs may induce in Parkinsonism reactivation of reticular-limbic-pineal systems involved in the generation of dreaming.

Sleep paralysis refers to episodes of inability to move during the onset of sleep or more commonly upon awakening. Patients often describe the sensation of struggling to move and may experience simultaneous frightening vivid hallucinations and dreams. Sleep paralysis and other manifestations of dissociated states of wakefulness and sleep, which reflect deficient monoaminergic regulation of neural modulators of REM sleep, have been reported in patients with multiple sclerosis (MS). A 40 year old woman with remitting-progressive multiple sclerosis (MS) experienced episodes of sleep paralysis since the age of 16, four years prior to the onset of her neurological symptoms. Episodes of sleep paralysis, which manifested at a frequency of about once a week, occurred only upon awakening in the morning and were considered by the patient as a most terrifying experience. Periods of mental stress, sleep deprivation, physical fatigue and exacerbation of MS symptoms appeared to enhance the occurrence of sleep paralysis. In July of 1992 the patient began experimental treatment with AC pulsed applications of picotesla intensity electromagnetic fields (EMFs) of 5Hz frequency which were applied extracerebrally 1-2 times per week. During the course of treatment with EMFs the patient made a dramatic recovery of symptoms with improvement in vision, mobility, balance, bladder control, fatigue and short term memory. In addition, her baseline pattern reversal visual evoked potential studies, which showed abnormally prolonged latencies in both eyes, normalized 3 weeks after the initiation of magnetic therapy and remained normal more than 2.5 years later. Since the introduction of magnetic therapy episodes of sleep paralysis gradually diminished and abated completely over the past 3 years. This report suggests that MS may be associated with deficient REM sleep inhibitory neural mechanisms leading to sleep paralysis secondary to the intrusion of REM sleep atonia and dream imagery into the waking state. Pineal melatonin and monoaminergic neurons have been implicated in the induction and maintenance of REM sleep and the pathogenesis of sleep paralysis and it is suggested that resolution of sleep paralysis in this patient by AC pulsed applications of EMFs was related to enhancement of melatonin circadian rhythms and cerebral serotoninergic neurotransmission.

A 50 year-old woman presented in January of 1995 with a prolonged history of symptoms of multiple sclerosis (MS) and was classified at the time with a remitting-progressive course. Her chief symptoms included slurring of speech, impairment of vision with intermittent diplopia, difficulties with gait and balance with spastic-ataxic gait, mental depression, insomnia, fatigue, impaired cognitive functions notably poor short term memory and recurrent urinary tract and sinus infections. An MRI scan showed multiple nodular demyelinating lesions scattered in the subcortical white matter and periventricularly of both cerebral hemispheres. Over the following 18 months, while receiving three treatment sessions per week with picotesla electro-magnetic fields (EMFs) which were applied extracranially, she showed a significant recovery in both physical and mental symptoms and additionally experienced decreased susceptibility to infections. In addition, the course of her disease appeared to have stabilized as opposed to the preceding 5 years during which time she experienced insidious, steady deterioration in her functioning. Despite this remarkable clinical recovery through the application of EMFs, and MRI scan obtained at the same diagnostic center 18 months after initiation of treatment with EMFs showed no changes in the number and size of the demyelinating plaques. These findings demonstrate lack of a correlation between recovery of symptoms and the number and extent of demyelinating plaques on MRI scan. It has been known since the days of Charcot in the latter half of the 19th century that in MS there is a great disparity between the histopathological changes of the disease and neurologic deficits. This report enhances the notion that demyelination may reflect an epiphenomenon of the disease.

Tourette's syndrome (TS), a chronic familial neuropsychiatric disorder of unknown etiology, is characterized clinically by the occurrence of motor and vocal tics and by the presence of a variety of neurobehavioral and neurocognitive abnormalities including hyperactivity, self-mutilatory behavior, obsessive-compulsive behavior, learning disabilities, and conduct disorder. Cognitive deficits related to right hemispheric dysfunction are common in TS patients accounting for decrements in visuospatial, visuoconstructional and visuomotor skills. An 11 year old boy with a 5 years history of TS exhibited during a routine neuropsychological assessment an unusual visuoconstructional disorder which previously has been observed in dyslexic children. Specifically, when instructed to draw a bicycle from memory, he drew spontaneously a design executed from the perspective of a bird's eye view. After receiving a 20 minute treatment session with picotesla range electromagnetic fields (EMFs) applied extracranially, this visuocontructional disorder was spontaneously reversed and he drew an elaborate and detailed bicycle positioned in profile. A placebo EMF treatment, which was administered prior to magnetic therapy, had no effect on this child's visuoconstructional disorder. During the ensuing week there was a marked reduction in the child's hyperactive behavior with attentuation of motor tics. Spontaneous drawing of a bicycle a week after the administration of magnetic therapy was executed in profile although some elements were presented from a bird's eye view. This case demonstrates the potential impact of treatment with picotesla EMFs in reversing specific cognitive deficits in TS related to right posterior hemispheric dysfunction.

Experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease, is widely considered as an animal model of multiple sclerosis (MS). It is believed that breakdown of the blood brain barrier (BBB) reflects the initial mechanism in the induction of EAE. It has been reported that while neonatally pinealectomized Wistar rats develop extensive pathological changes and severe neurologic deficits upon induction of EAE with allogeneic spinal cord in adjuvant, adult rats pinealectomized at 6 weeks of age appeared resistant to the induction of EAE. These findings suggest that: (a) the pineal gland influences the expression of EAE and, by inference, the integrity of the BBB; and (b) there is an age-related window of susceptibility to the development of EAE possibly related to the level of maturation of the pineal gland and functional integrity of the BBB. This age-related susceptibility to the development of EAE in rats may be relevant to the timing of aquisition of MS where a viral infection in childhood is thought to initiate the induction of autosensitization to myelin antigens. More specifically, it is suggested that the viral infection associated with the development of MS most likely is acquired in infancy prior to the establishment of the melatonin circadian rhythms between 3 and 9 months of age.

Hypotheses pertaining to the etiology of Parkinson's disease (PD) have suggested that the disease reflects an accelerated form of the normal aging process. Aging is associated with progressive failure of the pineal gland associated with a gradual decline in nighttime plasma melatonin secretion. The decline in melatonin secretion with age, at an average rate of 10-15% per decade, is considered a marker of brain aging in humans and estimations of plasma melatonin levels could be used to distinguish the processes of normal aging from pathological age-related changes. The accelerated aging hypothesis of PD is not supported by studies which have examined nocturnal melatonin secretion in drug naive Parkinsonian patients compared to age matched normal control subjects. Specifically, these studies have revealed no significant differences in the melatonin rhythms (i.e., peak nocturnal melatonin level and 24-hour melatonin output) between PD patients and normal age matched controls. On the other hand, melatonin secretion is significantly lower in Alzheimer's patients compared to age matched normal subjects. Collectively, it is suggested, on the basis of melatonin circadian rhythms, that Alzheimer's disease rather than PD is related to an accelerated aging process, a hypothesis which is supported by pathological and neurochemical studies.

Multiple sclerosis (MS) is associated with an increased risk of falling resulting from visual disturbances, difficulties with gait and balance, apraxia of gait and peripheral neuropathy. These factors often interact synergistically to compromise the patient's gait stability. It has long been recognized that walking involves a cognitive component and that simultaneous cognitive and motor operations (dual-task) such as talking while walking may interfere with normal ambulation. Talking while walking reflects an example of a dual-task which is frequently impaired in MS patients. Impaired dual-task performance during walking may compromise the patient's gait and explain why in some circumstances, MS patients unexpectedly lose their balance and fall. Frontal lobe dysfunction, which commonly occurs in MS patients, may disrupt dual-task performance and increase the risk of falling in these patients. This report concerns a 36 old man with remitting-progressive MS with an EDSS score of 5.5 who experienced marked increase in spasticity in the legs and trunk and worsening of his gait and balance, occasionally resulting in falling, when talking while walking. His gait and balance improved dramatically after he received two successive transcranial treatments, each of 45 minutes, with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density. Simultaneously, there was improvement in dual-task performance to the extent that talking while walking did not adversely affect his ambulation. In addition, neuropsychological testing revealed an almost 5-fold increase in word output on the Thurstone's Word-Fluency Test, which is sensitive to frontal lobe dysfunction. It is suggested that facilitation of dual-task performance during ambulation contributes to the overall improvement of gait and balance observed in MS patients receiving transcranial treatment with AC pulsed EMFs.

Visual evoked potential (VEP) studies are widely used for the diagnosis of multiple sclerosis (MS) and are also useful in monitoring the effects of various therapeutic modalities in the disease. Brief, extracerebral applications of picotesla (pT) range flux intensity electromagnetic fields (EMFs) of low frequency have been shown efficacious in the treatment of motor and cognitive symptoms in MS implying that this treatment modality improves action potential transmission in demyelinating pathways. This report documents three MS patients with a remitting-progressive course in whom two successive brief extracerebral applications of pT range EMFs caused an immediate increase (and normalization) of the amplitudes of the visual evoked response in the eye previously affected by optic neuritis. However, the pretreatment prolonged latencies of the evoked responses remained essentially unchanged after the administration of EMFs. Since the latency of the VEP reflects the degree of conduction velocity and the amplitude the degree of conduction block in demyelinating optic pathways, the report demonstrates that extracerebral applications of these EMFs may rapidly reverse conduction block in demyelinating fibers. Reversal of the conduction block, which is though to be related to changes in axonal Na+ and K+ channels and synaptic neurotransmitter release, accounts for the immediate improvement of vision and other neurological deficits observed in MS patients following exposure to these EMFs.

Pharmacological studies have implicated serotonergic (5-HT) neurons in the regulation of food intake and food preference. It has been shown that the urge to consume carbohydrate rich foods is regulated by 5-HT activity and that carbohydrate craving is triggered by 5-HT deficiency in the medical hypothalamus. Ingestion of carbohydrate foods stimulates insulin secretion which accelerates the uptake of tryptophan, the precursor of 5-HT and melatonin, into the brain and pineal gland, respectively. Thus, carbohydrate craving might be considered a form of "self medication" aimed at correcting an underlying dysfunction of cerebral 5-HT and pineal melatonin functions. A 51 year old woman with remitting-progressive MS experienced carbohydrate craving during childhood and adolescence and again in temporal association with the onset of her first neurological symptoms at the age of 45. Carbohydrate craving, which resembled the pattern observed in patients with seasonal affective disorder (SAD), was attenuated by a series of extracranial AC pulsed applications of picotesla (10(-12) Tesla) flux intensity electromagnetic fields (EMFs). It is suggested that AC pulsed EMFs applications activated retinal mechanisms which, through functional interactions with the medial hypothalamus, initiated an increased release of 5-HT and resynchronization of melatonin secretion ultimately leading to a decrease in carbohydrate craving. The occurrence of carbohydrate craving in early life may have increased the patient's vulnerability to viral infection given the importance of 5-HT and melatonin in immunomodulation and the regulation of the integrity of the blood brain barrier. The recurrence of this craving in temporal relation to the onset of neurological symptoms suggests that 5-HT deficiency and impaired pineal melatonin functions are linked to the timing of onset of the clinical symptoms of the disease. The report supports the role of experimental factors in the pathophysiology of MS.

5-HT2 receptors regulate sleep including yawning behavior. Ritanserin, a selective 5-HT2A receptor antagonist, increases the duration of slow wave in rats and humans. This effect is more pronounced during the light period when melatonin plasma levels are low; melatonin inhibits the sleep effects of ritanserin. These findings indicate that melatonin co-determines the effects of ritanserin on sleep. In a cohort of multiple sclerosis (MS) patients ketanserin, a selective 5-HT2A receptor antagonist, induces recurrent yawning particularly when administered in daytime. The frequency of yawning induced by the drug was modified by AC pulsed picotesla flux electromagnetic fields (EMFs) which affect melatonin secretion. Two MS patients are presented in whom the frequency of ketanserin-induced yawning was altered in opposite directions by these EMFs. The first patient, a 50 year old woman with a remitting-relapsing course, developed recurrent yawning and sleepiness after administration of ketanserin (10 mg, PO). Yawning was decreased dramatically during application of EMFs but was unaffected by a placebo EMFs treatment. The second patient, a 35 year old man with a chronic progressive course, manifested a single and brief yawn after administration of an equal dose of ketanserin. Yawning was increased dramatically during application of EMFs while remaining unchanged during a placebo EMFs treatment. These observations demonstrate a bidirectional effect of picotesla flux EMFs on ketanserin-induced yawning which may be related to differences in daytime melatonin plasma levels among MS patients. If validated by estimations of melatonin plasma levels in a larger cohort of patients the information derived from the effects of picotesla EMFs on ketanserin-induced yawning could be used to: (a) assess pineal melatonin functions in patients with MS; (b) indicate differences in pineal functions between male and female MS patients; and (c) indicate a relationship between plasma melatonin levels and the fatigue of MS.

It is estimated that 10-20% of patients with multiple sclerosis (MS) have a chronic progressive (CP) course characterized by an insidious of neurological deficits followed by steady progression of disability in the absence of symptomatic remission. No therapeutic modality has shown specific efficacy in the treatment of patients with CP MS and there are no data to indicate that any pharmacologic or other modality alters the clinical course of CP MS. Treatment with picotesla electromagnetic fields (EMFs) is a highly effective modality for the symptomatic management of MS including the chronic progressive form. In addition, this treatment also appears to alter the natural course of the disease in CP patients. A 36 year-old man experienced, at the age of 31, insidious weakness in the legs and several months later developed difficulties with balance with ataxia of gait. His gait abnormality progressed slowly over the following years and at the age of 35 he was severely disabled with spastic paraparesis and ataxia using a rolling walker for ambulation and a scooter for longer distances. In particular, his disability had progressed rapidly over the six months preceding the initiation of treatment with EMFs. He as classified have CP MS and his prognosis was considered extremely unfavorable due to the degree of cerebellar and pyramidal tract involvement and the rapid course of deterioration. In July 1995 the patient began experimental treatment with EMFs. While receiving three treatment sessions a week over 12 months he experienced improvement in cerebellar functions such as gait, balance and tremor as well as bowel and bladder functions, mood, sleep and cognitive function and resolution of diplopia, blurring of vision, dysarthria, paresthesias in the hands, and fatigue. Most remarkably, there was no further progression of the disease during the course of magnetic therapy. This case illustrated that treatment with EMFs, in addition to producing symptomatic improvement, also reverses the clinical course of CP MS.

Electrophysiological studies in behaving animals have shown the function of cerebral serotonin (5-HT) neurons to be altered in association with motor output in both the tonic and repetitive modes and also in relation to an orienting response. Brainstem 5-HT neurons increase their firing rate two to five-fold during repetitive motor activity to facilitate motor output while simultaneously suppressing transmission in sensory pathways. Reciprocally, during an orienting response motor activity is suppressed and 5-HT neuronal activity is inhibited to facilitate transmission of sensory information. These reciprocal changes in 5-HT neuronal activity serve to facilitate brainstem reticular sensory-motor integration which, due to 5-HT neurotransmission deficiency, may be disrupted in patients with multiple sclerosis (MS). For instance, MS patients are unable to process auditory information in the presence of competing ambient stimuli, while under a controlled laboratory environment they demonstrate unimpaired verbal information processing. This report concerns three MS patients who experienced rapid deterioration in balance resulting in falling when subjected, during ambulation, to distracting external auditory stimuli. After receiving a series of treatments with low frequency picotesla range intensity electromagnetic fields (EMFs), which were applied extracranially for brief periods, these patients experienced resolution of these symptoms with ambulation being unaffected by auditory stimuli. It is suggested that application of picotesla EMFs may restore abnormal reticular sensory-motor integration in MS patients with the effect being related to facilitation of 5-HT neurotransmission at both junctional (synaptic) and nonjunctional neuronal target sites.

Neuropsychological studies have demonstrated that Parkinson's disease (PD) is associated with various cognitive deficits ultimately leading in about 30% of patients to the development of dementia. These studies have demonstrated also a greater decrement of right hemispheric functions with visuospatial deficits occurring in up to 90% of PD patients. The Rey-Osterrieth Complex Figure (ROCF) Test has been employed in the assessment of right hemispheric functions and particularly for the evaluation of visuoconstructive abilities and short-term visual memory. I have demonstrated recently that external application of electromagnetic fields (EMFs) in the picotesla (pT) range intensity is an effective nonpharmacological modality in the management of the motor and cognitive deficits of Parkinsonism. In the present communication I present 3 fully medicated nondemented PD patients (mean age: 68 +/- 8.1 yrs; mean duration of illness: 9.0 +/- 4.0 yrs; mean disability on the Hoehn and Yahr scale: 3) who were tested on the ROCF Test before and after a series of treatments with EMFs. In response to the administration of EMFs the group demonstrated a mean of 23.1 +/- 13.6% improved performance on copy of the ROCF and a 39.3 +/- 13.4% improvement of short-term recall of the ROCF. These findings demonstrate that treatment with pT EMFs improves deficits in visuospatial functions and visual memory in Parkinsonism which usually remain unaffected during standard treatment with dopaminergic pharmacotherapy.

It has long been recognized that symptoms of multiple sclerosis (MS) wax and wane with fluctuations occurring on an hour to-hour basis throughout a 24 hour period. It has been proposed that changes in circadian core body temperature, which alter axonal conductivity, may account for the fluctuations of symptoms in MS. A 51-year-old man with MS is reported in whom visual acuity deteriorated throughout the course of the day only to improve again at night between 10:00 p.m. and 2:00 a.m. These changes in vision were unrelated to rest or physical activity, but appeared to coincide with the circadian secretion of melatonin which is coupled to the circadian temperature rhythms. Since melatonin lowers body temperature, it is hypothesized that the nocturnal rise in melatonin secretion was related to improvement in vision in this patient. This hypothesis is supported by the observation that administration of melatonin (3 mg, orally) at 2:00 p.m., when the patient experienced severe blurring of vision, resulted within 15 minutes in a dramatic improvement in visual acuity and in normalization of the visual evoked potential latency after stimulation of the left eye. Moreover, since the pineal gland is a thermoregulatory organ which functions to prevent excessive rise of body temperature, it is possible that since MS is associated with dysfunction of the pineal gland, these patients may experience diminished capacity to eliminate heat at rest or during physical activity with resultant elevation of body temperatures which may further compromise neurologic functions by causing failure of axonal conduction.

Gilles de la Tourette syndrome (GTS), a chronic, familial, neuropsychiatric disorder of unknown etiology, is characterized clinically by the presence of motor and vocal tics that wax and wane in severity over time and by the occurrence of a variety of neurobehavioral disturbances including hyperactivity, self-mutilatory behavior, obsessive compulsive behavior, learning disabilities, and conduct disorder. Pharmacological studies suggest that the tics of GTS result from dysfunction of monoaminergic systems, more specifically from increased dopaminergic activity due to postsynaptic dopamine receptor supersensitivity. However, given that striatal dopaminergic and cholinergic systems exhibit reciprocal antagonism in other movement disorders such as Parkinsonism and chorea, it is conceivable that the cholinergic system is implicated in the disease. In the present communication it is proposed that: (a) the emergence of motor and vocal tics in GTS is associated with increased central cholinergic activity; (b) cholinergic overactivity is involved in the manifestation of other symptoms in GTS including depression, sleep disorders, motion sickness, pain, sensory tics, and the waxing and waning course of the disease; (c) abnormalities of the cholinergic system support previous evidence linking GTS with delayed cerebral maturation in a subset of young patients; and (d) drugs which stimulate cholinergic receptors may exacerbate symptoms of GTS, and as with dopamine agonists, should be avoided in patients with GTS.

A 54 year-old woman was diagnosed with multiple sclerosis (MS) in 1985 at the age of 45 after she developed diplopia, slurred speech, and weakness in the right leg. A Magnetic Resonance Imaging (MRI) scan obtained in 1985 showed several areas of plaque formation distributed in the periventricular white matter and centrum semiovale bilaterally. Coincident with slow deterioration in her condition since 1990 a second MRI scan was obtained in 1991 which showed a considerable increase in the number and size of plaques throughout both cerebral hemispheres, subcortical white matter, periventricularly and brainstem. In 1994, the patient received treatment with Interferon beta- 1b (Betaseron) for 6 months with no improvement in symptoms. However, following two successive extracranial applications of pulsed electromagnetic fields (EMFs) in the picotesla (pT) range each of 20 minutes duration the patient experienced an immediate improvement in symptoms most dramatically in gait, balance, speech, level of energy, swallowing, mood, and vision. On a maintenance program of 3 treatments per month the patient's only symptom is mild right foot and leg weakness. The report points to the unique efficacy of externally applied pT range EMFs in the symptomatic treatment of MS, indicates a lack of an association between the extent of demyelinating plaques on MRI scan and rate and extent of recovery in response to EMFs, and supports the notion that dysfunction of synaptic conductivity due to neurotransmitter deficiency particularly of serotonin (5-HT) contributes more significantly to the development of MS symptoms than the process of demyelination which clinically seems to represent an epiphenomenon of the disease.

It has been suspected that hormonal factors contribute to the etiology and pathogenesis of multiple sclerosis (MS). A direct relationship between MS and endocrine functions is suggested by changes in disease activity during the phases of the menstrual cycle. A subset of women with MS experience premenstrual worsening of symptoms which improve dramatically with the onset of menstruation. The biological mechanisms underlying these changes in disease activity are unexplained but may be related to cyclical fluctuations in gonadal sex steroid hormones, abrupt changes in the activity of the endogenous opioid peptides and fluctuations in plasma melatonin levels which affect neuronal excitability and immune functions. Extracerebral application of weak electromagnetic fields (EMFs) in the picotesla range intensity has been reported efficacious in the treatment of MS with patients experiencing sustained improvement in motor, sensory, autonomic, affective and cognitive functions. The present report concerns two women with chronic progressive stage MS who experienced, coincident with increasing functional disability, regular worsening of their symptoms beginning about a week before menstruation and abating with the onset of menstruation. These symptoms resolved two months after the initiation of treatment with EMFs. The report supports the association between the endocrine system and MS and indicates that brief, extracranial applications of these magnetic fields modifies the activity of neuroendocrine systems which precipitate worsening of MS symptoms premenstrually.

Since the discovery of melatonin as the principal hormone of the pineal gland in 1963, scientists have come to recognize that melatonin is a "master hormone" involved in the control of circadian rhythms and other biological functions. Although little is known about the influence of the pineal gland on motor control, important clues may be obtained by considering the pattern of melatonin secretion during the sleep cycles and particularly during rapid eye movement (REM) sleep when melatonin plasma levels are at their lowest. Since REM sleep is characterized by the occurrence of profound atonia which results in an almost complete paralysis of striated muscles, it is suggested that there might be a causal relationship between inhibition of melatonin secretion during REM sleep and the development of REM sleep atonia. This relationship is supported by the findings that melatonin regulates the activity of brainstem serotonin (5-HT) neurons which characteristically cease to fire during REM sleep and which faciliate the development of REM sleep atonia. Moreover, as the muscular atonia of REM sleep is physiologically and pharmacologically indistinguishable from cataplexy, it is possible that the pineal gland also influences to the development of cataplexy. Cataplexy is an ancillary symptom of narcolepsy and also occurs in multiple sclerosis (MS). In fact, it is believed that several of the neurological symptoms experienced by patients with MS such as weakness in the legs, feeling of collapsing knees, paroxysmal sudden falling, weakness in the neck, extreme fatigue, intermittent paresthesias, slurring of speech and intermittent blurring of vision, which often are exacerbated by stress and other emotional influences, may reflect the manifestations of cataplexy. Thus, several of the clinical features of MS may reflect a dissociated state of wakefulness and sleep and may improve by the administration of anticataplectic drugs.

Recently, I reported that extracranial treatment with picoTesla range magnetic fields (MF) is an effective, safe, and revolutionary modality in the management of Parkinsonism including those patients manifesting levodopa-induced motor complications. This treatment, which has emerged as a potentially more advantageous modality than pharmacologic therapy, also produces improvements in nonmotor aspects of the disease including mood, cognitive functions, sleep, pain, appetite, autonomic functions, and sexual behavior, which are usually minimally, if at all, ameliorated by long term therapy with levodopa or anticholinergic agents. The present communication concerns a 69 year old Parkinsonian patient who, following a series of two treatments with extracranial picoTesla range MF on two separate days, improved to the point where he was able to discontinue most of his antiparkinsonian medications for a period of two weeks without experiencing deterioration in symptoms. On the third week he began to develop recurrence of symptoms and resumed taking his regular medications. At the end of the fourth week the patient received a series of four magnetic treatments on four successive days after he completely discontinued his antiparkinsonian medications. During this period he experienced a remarkable improvement in motor disability as well as in cognitive functions (i.e., visuospatial performance), mood, sleep, appetite, bowel functions and resolution of pain in the lower extremity. This report attests to the antiparkinsonian efficacy of picoTesla range MF and suggests that this treatment, when applied on a regular basis, may reduce the requirement for antiparkinsonian medications. This observation, when confirmed in a larger cohort of patients, may carry important implications for the therapy of Parkinsonism as it may offer an alternative treatment for patients who develop levodopa failure or experience intolerable side effects from dopaminergic medication. The observation that magnetic treatment improved the patient's symptoms while being off dopaminergic therapy supports the role of nondopaminergic mechanisms in the pathophysiology of Parkinsonism.

Multiple sclerosis (MS) is the most common of the demyelinating diseases of the CNS. The clinical course and prognosis of the disease are variable. Characteristically, the illness tends to progress in a series of relapses and remissions. Over the years there is a tendency for the patient to enter a phase of slow and steady deterioration of neurologic function. In about 10%-20% of patients, the course of the disease is not punctuated by a fluctuating course, but rather by an inexorable progression from the onset. The pineal gland has been implicated recently in the pathogenesis and clinical course of MS. Since MS is generally a chronic progressive disorder, we predicted an association between duration of illness and the activity of the pineal gland. To investigate this hypothesis further, we studied nocturnal plasma melatonin levels in relation to duration of illness in a cohort of 32 MS patients (4 men, 28 women; mean age: 41.1 years; SD = 11.1; mean duration of illness: 13.1 years; SD = 12.4) randomly selected from consecutive hospital admissions to a Neurology service for exacerbation of symptoms. For the purpose of comparison, we also studied in the sample serum prolactin levels. The cohort included 7 patients in whom the duration of illness since onset of first neurological symptoms wasor = 5 years (mean: 3.0 years +/- 1.1) and a cohort of 25 patients in whom the duration of illness was5 years (mean: 15.6 years +/- 12.7).(ABSTRACT TRUNCATED AT 250 WORDS)

The occurrence of cognitive impairment including visuoperceptive and visuospatial deficits have long been recognized to occur in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. In MS visuospatial and visuoperceptive deficits have been attributed to the presence of diffuse demyelinating plaques which "disconnect" the brainstem reticular formation and other subcortical structures involved in attention and arousal from cortical areas thus causing a state of hypoarousal. It has been reported recently that brief external applications of alternating pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity improved visuoperceptive and visuospatial functions in MS patients. The present communication concerns three female patients with chronic progressive course of MS (mean age: 52.3 +/- 2.0 yrs; mean duration of illness: 17.6 +/- 10.2 yrs) who, on tests of free drawings, demonstrated visuospatial hemi-inattention as a feature of more global cognitive deterioration. In all patients brief applications of EMFs rapidly reversed this cognitive deficit. These findings support prior observations demonstrating that pT EMFs may bring about reversal of certain cognitive deficits in MS patients which, to my knowledge, remain unaffected by any other treatment modality.

Visuoperceptive and visuomotor deficits are among the most frequently encountered abnormalities in neuropsychological testing of patients with Parkinson's disease, being present in up to 90% of cases. Clinically, the presence of visuoperceptive and visuomotor impairment may not be noted by Parkinsonian patients but may contribute to various functional disabilities including difficulties operating a vehicle, ambulating, and dressing. The present communication concerns five medicated Parkinsonian patients who responded to extracranial treatment with magnetic fields in the picotesia range intensity with improvement in motor, behavioral, and autonomic functions as well as visuoconstructional tasks as demonstrated on the Bicycle Drawing test. Specifically, prior to treatment with magnetic fields these patients failed to draw the spokes in the wheels of a bicycle that extended completely to the periphery of the rim. I considered this observation to reflect a specific visuoconstructional deficit inherent to the Parkinsonian disease process. This visuoconstructional impairment was reversed, however, by external applications of magnetic fields. The report supports prior observations demonstrating that picotesla range intensity magnetic fields may bring about reversal of specific cognitive deficits in Parkinsonian patients.

Extracranial treatment with magnetic fields (MF) in the picoTesla range has been shown an efficacious treatment modality in the management of Parkinsonism. The mechanisms by which such extremely weak MF improve Parkinsonian symptoms are unknown. As the pineal gland has been shown to function as a "magnetosensor" and since exposure to various intensities of MF disrupts melatonin secretion, it has been proposed that the beneficial effects of MF in Parkinsonism are partly mediated through the actions of pineal melatonin. Animal studies indicate that externally applied MF also influence the activity of the opioid peptides which have been implicated in a broad range of pathological conditions including Parkinsonism. To explore whether the beneficial effects of MF in Parkinsonism involve the mediation of the opioid systems and following informed consent, we administered the opiate receptor antagonist naltrexone (50 mg, P.O.) to a Parkinsonian patient after he showed improvement of symptoms with application of MF. Results of the trial showed that naltrexone partially reversed the antiparkinsonian effects of MF thus suggesting that opioid peptides are involved in mediating the clinical effects of these extremely weak MF in Parkinsonism. These results also suggest that intact opioid systems may be required for a full expression of the antiparkinsonian effect of picoTesla range MF.

Calcification is a known morphological feature of the pineal gland. The mechanisms underlying the development of pineal calcification (PC) are elusive although there is experimental evidence that calcification may be a marker of the past secretory activity of the gland and/or of degeneration. The increased incidence of PC with aging suggests that it may reflect cerebral degenerative changes as well. In a recent Editorial in this Journal it was proposed that the pineal gland is implicated in the pathogenesis of multiple sclerosis (MS). Cerebral atrophy, which can be demonstrated on CT scan, is a common feature of MS resulting from demyelination and gliosis. If PC is a marker of a cerebral degenerative process, then one would expect a higher incidence of calcification of the gland in patients with cerebral atrophy compared to those without cerebral atrophy. To test this hypothesis, we studied the incidence of PC on CT scan in a cohort of 48 MS patients, 21 of whom had cerebral atrophy. For the purpose of comparison, we also assessed the incidence of choroid plexus calcification (CPC) in relation to cerebral atrophy. PC was found in 42 patients (87.5%) and its incidence in patients with cerebral atrophy was significantly higher compared to the incidence in patients without cerebral atrophy (100% vs. 77.7%; p < .025). In contrast, CPC was unrelated to cerebral atrophy or to PC thus supporting the notion of a specific association between the pineal gland and the pathogenesis of MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Paroxysmal attacks of itching constitute a rare sensory symptom of multiple sclerosis (MS). It is generally thought that paroxysmal itching, a form of subthreshold pain sensation, is caused by transversely spreading ephaptic activation (i.e., activation via an artificial synapse) of axons within a partially demyelinated lesion in fiber tracts in the CNS, most commonly in the spinal cord. In MS, attacks of paroxysmal itching have been reported to occur either as the initial symptom of the disease or at the onset of an acute relapse. I present two female MS patients aged 36 and 40 years in whom paroxysmal itching was a prominent sensory symptom which occurred at the onset of treatment with external picoTesla range magnetic fields (MF) and coincident with the process of neurologic recovery. This report suggests that picoTesla range MF may cause activation of neuronal transmission along partially demyelinated axons of pain conduction in the spinal cord. The occurrence of rapid neurologic recovery with initiation of treatment with MF supports the notion that impaired synaptic conductivity rather than demyelination underlies some of the neurologic deficits of MS.

The association between degeneration of the nigrostriatal dopamine (DA) system and the motor manifestations of Parkinson's disease (PD) provided the impetus for the development of DA replacement therapy. However, clinical experience has demonstrated that DA-ergic drugs, while attenuating the motor symptoms of PD, have little or no consistent effect on the mental and cognitive symptoms of the disease which are thought to be related partly to degeneration of the meso-cortico-limbic DA system. Thus, failure of DA-ergic drugs to improve the mental and cognitive deficits of PD indicates that these agents cannot fully restore DA functions in the meso-cortico-limbic circuits. The present communication concerns five fully medicated Parkinsonian patients in whom application of a series of treatments with electromagnetic fields (EMF) of extremely low intensity (in the picotesla range) and frequency (5-8Hz) produced a dramatic improvement in performance on Thurstone's World-Fluency Test, a sensitive marker of frontal lobe functions. These findings suggest that in contrast to DA replacement therapy application of low intensity EMF may improve frontal lobe functions in patients with PD presumably by augmenting DA activity in the mesocortical system. As deficiency of the frontal DA system has been implicated also in the development of akinesia and freezing in PD these observations may explain the beneficial effects of EMF on the motor manifestations of the disease.

The occurrence of cognitive deficits in patients with multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory" in his patients and subsequently Gowers (1893) described "failure of memory." The presence of cognitive deficits in MS may be a major cause of disability which is often severe enough to preclude employment. Impairment of memory including visual memory is one of the most common features of the dementia of MS and may be evident in early stages of the disease. Disturbances of visuospatial and visuomotor functions are also commonly encountered in MS patients reflecting the multiplicity of lesion sites in the disease. Recently, I have reported that treatment with magnetic fields (MF) in the picoTesla range is an efficacious modality in the management of MS and have demonstrated improvement in visuospatial functions with this treatment modality. In the present communication I present four additional patients with MS in whom application of these extremely weak MF produced an improvement in visual memory as well as visuospatial and visuomotor functions. The data presented demonstrate the unique efficacy of this treatment modality in reversing some of the cognitive deficits associated with MS.

Respiratory dyskinesia, a syndrome characterized by an irregular respiratory rate, tachypnea, and grunting, is a serious complication of chronic neuroleptic therapy. It frequently occurs in elderly women and is commonly associated with clinical features of Tardive dyskinesia (TD). Respiratory dyskinesia initially was considered to be a rare complication of chronic neuroleptic treatment, but more recent reports indicate that respiratory abnormalities are common in patients treated with antipsychotic medications. The appropriate management of patients with respiratory dyskinesia has not been determined as the underlying pathophysiology is incompletely understood. We present a schizophrenic patient on long term antipsychotic therapy who presented with respiratory dyskinesia associated with symptoms of TD and tardive Tourette's syndrome which emerged coincident with an abrupt withdrawal of neuroleptic therapy. In this patient, external application of picoTesla range magnetic fields (MF) produced rapid attenuation in the severity of respiratory and motor dyskinesias. As the pineal gland is considered a magnetosensor and since exposure of experimental animals and humans to external MF alters melatonin secretion, we then propose that the beneficial effects of MF involve the mediation of the pineal gland which has been implicated previously in the pathophysiology of drug-induced movement disorders including TD.

It has been estimated that about 75% of patients diagnosed with multiple sclerosis (MS) have tremor which can be exceedingly disabling. The most common tremor observed in patients with MS is a cerebellar intention tremor ('kinetic tremor') although postural tremor ('static tremor') is also common and often extremely incapacitating. Currently there is no effective medical treatment for the tremor of MS which, in some severe cases, may be abolished by stereotactic thalamotomy. It was reported recently that extracranial application of brief AC pulsed electromagnetic fields (EMFs) in the picotesla (pT) range produced improvement in motor and cognitive functions in patients with MS. The present communication concerns three MS patients with a chronic progressive course of the disease (mean age: 39.3 +/- 8.3 years; mean duration of illness: 11.3 +/- 3.2 years) in whom brief external applications of pulsed EMFs of 7.5 pT intensity reduced intention and postural tremors resulting in significant functional improvement. The report suggests that these extremely low intensity EMFs are beneficial also in the treatment of tremors in MS and that this treatment may serve as an alternative method to stereotactic thalamotomy in the management of tremor in MS. The mechanisms by which EMFs attenuate the tremors of MS are complex and are thought to involve augmentation of GABA and serotonin (5-HT) neurotransmission in the cerebellum and its outflow tracts.

Several studies suggest that disturbances of serotonin (5-HT) functions may be involved in the pathophysiology of hallucinations in schizophrenia. It is now well established that the choroid plexus (CP) is innervated by serotonin (5-HT) neurons, which may regulate its activity, and it is possible that decreased 5-HT functions may facilitate the process of its calcification. It is thus conceivable that calcification of the CP may be associated with hallucinations in schizophrenia. I studied in 18 chronic schizophrenic patients the association of CP calcification (CPC) size as ascertained from CT scan, to severity of hallucinations and, for comparison, to four other positive symptoms as well as global psychopathology score. Analysis of variance indicated that CPC size was specifically associated with hallucinations (p.001) and none of the other psychopathology measures. These findings reveal a relationship between CPC and hallucinations in schizophrenia and suggest that the former may be a neuroradiological marker of hallucinations in the disease.

Impairment in perceptual motor or visuospatial tasks is among the most frequently encountered abnormality in neuropsychological testing of patients with Parkinson's disease, being present in up to 90% of cases. Visuoperceptive deficits can result from cortical and subcortical lesions involving the right hemisphere, thalamus, and basal ganglia and are thought to reflect a defect in attentional-arousal mechanisms induced by lesions that interrupt a cortical-limbic-reticular activating loop. Clinically, the presence of visuoperceptive impairment may not be noted by Parkinsonian patients but may contribute to various disabilities including difficulty driving a vehicle and difficulties performing daily tasks which require intact visuospatial abilities (i.e., walking, dressing, drawing and copying designs). The present communication concerns two fully medicated Parkinsonian patients who responded to extracranial treatment with picoTesla range magnetic fields (MF), behaviorally and also demonstrated rapidly and dramatically enhanced visuoperceptive functions as demonstrated on various drawing tasks. These findings demonstrate the efficacy of extremely weak MF in enhancing cognitive functions in patients with Parkinson's disease.

Treatment with picoTesla magnetic fields recently has been reported to attenuate symptoms of Parkinson's disease (PD). The mechanisms by which weak magnetic fields ameliorate Parkinsonian symptoms are unknown. There is evidence that the pineal gland is a "magnetosensor" in the brain since in experimental animals exposure to external magnetic fields alters the firing rate of pineal cells and induces inhibition of melatonin secretion. Hence, the clinical effects of weak magnetic fields in PD likewise may involve the mediation of the pineal gland. Animal data indicate that the pineal gland is involved in the regulation of glucose metabolism and that exogenous administration of melatonin induces an hyperglycemic effect. To investigate the hypothesis that the pineal gland mediates the therapeutic properties of weak magnetic fields in PD, I studied the effects of orally administered melatonin (3.0 mg) followed by a 6 minute application of low intensity external weak magnetic fields (7.5 picoTesla) on blood glucose levels in two Parkinsonian patients. In both patients melatonin challenge produced a moderate hyperglycemic effect which was reversed by subsequent stimulation with weak magnetic fields. These findings support the hypothesis that weak magnetic fields inhibit melatonin secretion and that the antiParkinsonian properties of weak magnetic fields are mediated partially via the inhibition of melatonin secretion. Furthermore, these data suggest that melatonin receptor antagonists could be beneficial as an adjunctive treatment in PD and highlight the importance of the pineal-hypothalamic axis in the pathophysiology of the disease as well as in the mechanisms of action of antiParkinsonian drugs.

Multiple sclerosis (MS) is characterised by the occurrence of patchy CNS demyelinating lesions, leading to various degrees of motor, sensory, affective, and cognitive deficits. MS is associated also with an increased risk of suicide accounting for a substantial rate of death among these patients. Post-mortem studies in suicide victims with various psychiatric disorders demonstrate a decreased concentration of serotonin (5-HT) and its metabolites in the brain. Since 5-HT is a precursor in the synthesis of melatonin and as pineal melatonin content was found to be low in suicide victims, we predicted lower melatonin secretion in suicidal versus non-suicidal MS patients during an acute exacerbation of symptoms. To test this hypothesis, we investigated nocturnal plasma melatonin levels in a cohort of 28 relapsing patients who were admitted consecutively to an inpatient Neurology service, 6 of whom had a history of suicide attempts and were having suicidal ideation at the time of admission. While both cohorts of patients were not distinguishable on any of the demographic data including use of psychotrophic drugs on the day of admission to hospital, the mean melatonin level in the suicidal group was significantly lower than in the control group (19.0 pg/ml +/- 11.9 versus 45.5 pg/ml +/- 27.1; p.05). These findings support the prediction of the study implicating the pineal gland in the pathogenesis of suicidality in MS and reinforce the concept that a biological rather than a reactive etiology underlies the development of psychiatric symptoms in MS.

Drawing tasks, both free and copied, have achieved a central position in the neuropsychological evaluation of constructional abilities in brain injured patients. The Rey-Osterrieth Complex Figure Test was devised in early 1940s as a tool to investigate perceptual organization and visual memory. The Bicycle Drawing Test is used as a measure of mechanical reasoning as well as visuographic functioning. Recent reports have demonstrated that extracranial treatment with magnetic fields (MF) in the picoTesla range improves constructional abilities including visuoperceptive functions in Parkinsonian patients. To evaluate further the effects of these extremely weak MF on cognitive functions in Parkinsonism, I investigated in a 69 year old fully medicated Parkinsonian patient the influence of a single, extracranial application of MF on the patient's performance on the Complex Figure (copy and recall) as well as the Bicycle Drawing Test. Results of the trial showed that a 30 minute application of MF produced a dramatic improvement in the patient's ability to copy and recall the Complex Figure. This treatment was also associated with a marked improvement in the performance of bicycle drawing with reversal of the Parkinsonian micrographia. Collectively, these findings demonstrate that this treatment modality may reverse some of the cognitive impairments associated with Parkinsonism which usually are not improved by treatment with dopaminergic or anticholinergic medications.

A 55 year old woman with multiple sclerosis presented with a 5 week history of an exacerbation of symptoms. Prominent among these symptoms was trigeminal neuralgia, migraine headaches, blurring of vision, and ataxia of gait. While treatment with carbamazepine (TegretolR) (800 mg/d) and oral prednisolone (15 mg/d) over a 4 week period produced no improvement in symptoms, externally applied magnetic fields (MF) (7.5 picoTesla; 5 Hz) placed over the scalp for a 7 minute period on three different days resulted in a complete resolution of symptoms within two weeks of initiation of treatment. Partial relief of the neuralgic pain and headaches was obtained immediately after completion of the first treatment indicating that resolution of symptoms was related to the effects of MF and not to a spontaneous remission. This is the first report demonstrating the clinical efficacy of pico Tesla range MF in rapidly resolving an acute relapse of MS.

Epidemiological studies suggest an apparent protective effect of cigarette smoking on the risk of Parkinson's disease. There is also a report suggesting that patients with Parkinson's disease who smoke are less likely to develop dementia. I investigated the relationship of smoking to the severity of cognitive functions and presence of drug-induced parkinsonism in a group of 111 neuroleptic-treated chronic institutionalized schizophrenic patients. Patients who smoked had significantly less cognitive impairment (p

Although schizophrenia usually emerges at mid to late-adolescence, it has been estimated that almost 20% of schizophrenic patients develop their first symptoms in mid to late life (late-onset schizophrenia). The biological characteristics that distinguish patients with early onset from those with late-onset schizophrenia have not been well delineated. A subgroup of neuroleptic-treated schizophrenic patients develops tardive dyskinesia (TD) and the majority of these patients are unaware of their movements. To investigate whether early and late-onset schizophrenic patients with TD could be differentiated on the basis of awareness of involuntary movements, we compared the prevalence of awareness of these abnormal movements in patients with early (N = 40) and late-onset (N = 15) schizophrenia. We found a significantly higher prevalence of awareness of involuntary movements in patients with late-onset schizophrenia as compared to those with an earlier age of onset (86.6% vs. 25.0%, p.0001). In a second study, we investigated whether early and late-onset schizophrenia could be differentiated on the basis of dopamine functions in the mesolimbic system. Since tobacco addiction is mediated via limbic dopaminergic functions, we investigated the prevalence of tobacco addiction in patients with early (N = 51) and late-onset (N = 13) schizophrenia. We found a significantly lower prevalence of tobacco addiction in patients with late-onset schizophrenia as compared to those with an earlier age of onset (15.4% vs. 54.9%; X2 = 6.49; p.01). Our findings support the notion that distinct pathophysiological mechanisms underlie the development of early and late-onset schizophrenia.

A 72 year-old female patient is presented in whom delusional depression, a possible distinct subtype of depressive illness characterized by a selective decrease of cerebrospinal fluid (CSF) norepinephrine (NE) metabolism, preceded the onset of Parkinsonism by several years. The report suggests that delusional depression may be a particular manifestation of depressive illness in Parkinsonian patients. In addition, since the activity of plasma and cerebrospinal fluid (CSF) dopamine beta-hydroxylase (DBH) is genetically determined, the co-occurrence of delusional depression and Parkinsonism in this patient may be related to a common underlying genetic defect that expresses itself biochemically by reduced cerebral NE metabolism.