Search

Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA. Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry.

Background and purpose Sleep disorders have been mentioned since the first descriptions of extrapyramidal diseases in James Parkinson's Essay on the Shaking Palsy, but only recently they have become the subject of attention, thanks to new acquisitions in clinical knowledge and electroencephalographic technology. In the late 1960s, the introduction of L-dopa permitted comparison of sleep patterns in drug-naive patients before and after therapy in conditions very similar to experimental ones. Historically, we can recognise two major lines of study, one dealing with descriptions of sleep behaviours modified by drugs and the other with polysomnographic sleep research carried out before and after treatment. Patients and methods The data obtained from the first polysomnographic studies led to the definition of sleep macro- and microstructure in patients suffering from Parkinson's disease, but the interpretation of drug-induced changes was not unequivocal. Results According to some authors, the improvement in sleep architecture was due mainly to improvement of nocturnal motor impairment. Other researchers suggested a primary sleep dysfunction caused by specific neurodegenerative processes in the brain structures regulating the sleep–wake cycle. Conclusions The latter hypothesis has recently been supported by the observation that distinct sleep disorders, such as REM behaviour disorder or restless legs syndrome, often herald extrapyramidal diseases or are a frequent adjunctive complaint for these patients.

Myotonic dystrophy (DM) is a multisystemic disease caused by the expansion of a CTG repeat, located in the 3'-untranslated region of the DMPK gene. The number of CTG repeats broadly correlates with the overall severity of the disease. However, correlations between CTG repeat number and presence/absence or severity of individual clinical manifestations in the same patients are yet scarce. In this study the number of CTG repeats detected in blood cells of 24 DM subjects was correlated with the severity of single clinical manifestations. The presence/absence of muscular atrophy, respiratory insufficiency, cardiac abnormalities, diabetes, cataract, sleep disorders, sterility or hypogonadism is not related to the number of CTG repeats. Muscular atrophy and respiratory insufficiency are present with the highest frequency, occurring in 96 and 92% of the cases, respectively. A significant correlation was found with age of onset (r = -0.57, p

Thunderclap headache is well known to be a presenting feature of a variety of causal events. Indeed, a primary form is considered in the International Classification of Headache Disorders-II, but such diagnosis must be made only after exclusion of a possible secondary cause. We report a case of late-onset idiopathic aqueductal stenosis presenting with thunderclap headache, in the absence of abnormal neurological findings or indirect signs of raised intracranial pressure. The patient recovered completely after endoscopic third ventriculostomy. This case indicates primary aqueduct stenosis as a possible, never previously reported, cause of thunderclap headache.

Middle-latency somatosensory evoked potentials (MLSEPs) were recorded from 19 scalp electrodes in ten male patients with the fragile X (fraX) syndrome and nine normal controls. One fraX patient was found presenting the so-called "giant" MLSEPs with an amplitude of N60 of about 60 microV and of 40 microV after stimulation of the right and left median nerves, respectively. Tapping of the right hand, in the same patient, induced the appearance of left parietal evoked EEG spikes. These findings further support the already suggested similarity between the epileptic picture of several fraX patients with that of the benign childhood epilepsy with centrotemporal spikes. Color mapping of the MLSEPs recorded in the remaining nine patients, when compared with the control group, showed an abnormally large N30 over the frontal regions, together with an increase in amplitude of P27, over the parietal areas, and of N60 and P100 which also presented abnormal field distributions, being represented preferentially over the frontal regions. These data could suggest the existence of a cortical dysfunction mostly involving the frontal lobes (supplementary motor area, in particular) in the fraX syndrome which could support many behavioral changes usually observed in these patients.

Summary Middle-latency somatosensory evoked potentials (MLSEPs) were recorded from 19 scalp electrodes in 19 patients with Down's syndrome (DS), in 13 age-matched normal controls and in 11 aged normal individuals. DS patients showed an increase in amplitude of P22, N30, P45, and N60. P100 latency was significantly shortened. After this potential, DS subjects showed the occurrence of a high voltage negative potential at around 100–110 msec followed by another high-voltage positive deflection; both these components showed a frontal-central distribution and were not observed in the two control groups. MLSEPs of DS subjects show peculiar alterations which could be supported by particular neurometabolic and/or neuropathologic changes.

EEG during wakefulness and sleep and somatosensory evoked potentials from the median nerve were recorded in a 3 year-old boy with hyperekplexia and his close relatives (parents and two sisters). Centro-temporal spikes during sleep were found in the patient and in the older sister, while somatosensory evoked potentials, in the patient, showed abnormally high amplitude over the centroparietal regions. Pathophysiological mechanisms of hyperekplexia are discussed and the existence of symptomatic forms is suggested.

Brainstem auditory evoked potentials were recorded in 4 subjects and pattern reversal evoked potentials in 1 subject, all with tuberous sclerosis. Alterations were found (absence or delay of components and prolonged interpeak intervals) which may suggest impaired nervous conduction also at brainstem level in patients with tuberous sclerosis.

To evaluate the accuracy of hospital discharge data as a source of Amyotrophic Lateral Sclerosis (ALS) cases for epidemiological studies or disease registries, a validation study was performed. All records of patients discharged in 2005 and 2006 with principal or secondary International Classification of Diseases, 9th rev., Clinical Modification (ICD 9 CM) diagnosis code of ALS (335.20), other anterior horn cell disease (335), spinal cord disease (336), hereditary and idiopathic peripheral neuropathy (356), inflammatory and toxic neuropathy (357), myoneural disorders (358), muscular dystrophies and myopathies (359), were selected from the electronic archive of discharge data of the University Hospital of Udine, Friuli Venezia Giulia Region, North East Italy. Corresponding clinical documentation was reviewed to ascertain the presence of El Escorial criteria, the gold standard. Sensitivity of the ICD 9 CM discharge code 335.20 was 93% (95%CI: 82–99%) and decreased to 91% (95%CI: 77–98%) when suspect ALS was excluded. Specificity was 99% (95%CI: 97–99%). The ICD 9 CM discharge code 335.20 can identify a high percentage of hospitalizations of patients truly affected by ALS and of patients with no ALS, among selected neurological diagnostic codes. To ensure complete ALS case ascertainment, prospective population-based registries or epidemiologic studies require active prospective surveillance and use of multiple sources, among them hospital discharge archives can provide accurate information.

We report a case of rhabdomyolysis with severe generalized weakness and muscle pain after administration of ritodrine hydrochloride, in a pregnant patient without history of neuromuscular disease. Laboratory tests showed an increase of blood CK value and myoglobinuria. An electromyography was performed, revealing a typical myogenic pattern and diffuse denervation activity. Muscular biopsy allowed to rule out inflammatory and metabolic myopathy. After delivery, the patient underwent intensive rehabilitation with progressive improvement of her clinical situation, until complete recovery. Three months later, both neurological assessment and CK levels were normal. This case highlights that rhabdomyolysis has to be considered even in patient treated with ritodrine alone and without history of neuromuscular disease. Therefore, muscular symptoms and CK levels should be monitored in women treated with ritodrine for premature labour.

Background.— Few studies in adolescents deal with the level of agreement between questionnaire and interview information in relation to headache symptoms. Objective.— To evaluate the validity of a self-administered questionnaire on headache for use in epidemiological studies of Italian high school students. Methods.— The questionnaire incorporated all items required for diagnosing migraine according to the criteria from the 2004 International Classification of Headache Disorders. The migraine diagnoses obtained from questionnaires were validated against the gold standard diagnoses by a headache specialist. Results.— Out of 104 students answering the questionnaires, 93 (89.4%) participated in extensive semi-structured interviews by a neurologist. The chance-corrected agreement rate (kappa) was 0.66, which is considered good. The questionnaire-based migraine diagnosis had a sensitivity of 67.3%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 73.3%. Conclusions.— The results indicate that our self-administered questionnaire may be an acceptable instrument in determining the prevalence of migraine sufferers in the northeast Italy adolescent population, useful in identifying subjects with “definite” migraine.

Summary Polygraphic sleep recordings (EEG, EMG, and EOG) were performed in two groups of epileptic subjects, six with fragile-X syndrome and six with symptomatic epilepsy. Recordings were visually scored for sleep stages and number of spikes/min. Subjects with fragile-X syndrome showed a well defined pattern of production of interictal epileptiform activity with the lowest values during REM sleep; symptomatic epileptic subjects showed less defined and more variable spike/min diagrams. The spectral analysis of the outline of such diagrams confirmed these differences showing shorter periodicties (80–100 min) in the fragile-X group compared to those of the symptomatic group (160–220 min). Finally, a model with multiple feedback circuits is proposed in order to explain the different patterns observed.

Anticancer drugs may cause neurological toxicity involving the central nervous system. Patients receiving anticancer treatment may develop encephalopathy, extrapyramidal reactions, seizures, cerebellar dysfunction, retinopathy, cerebral venous thrombosis, myelopathy, cognitive impairment, and psychiatric symptoms. Physician should carefully evaluate neurological signs and symptoms in order to recognize these drug-related adverse reactions. In this review we aimed at presenting different neurological complications of anticancer drugs and their management. PUBMED search was performed in order to retrieve all articles and case reports dealing with central nervous system toxicity related to anticancer treatments.

Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington's disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and age-matched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and pre-manifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD.

Paraneoplastic neurological syndromes are a rare complication of breast cancer. Nevertheless, they may be clinically relevant leading to neurological impairment. Clinicians should be aware that these neurological disorders could even precede the diagnosis of breast cancer. Here we present the case of a female patient with advanced breast cancer who developed paraneoplastic sensorimotor neuropathy. Treatment with capecitabine lead to clinical amelioration. A review of the literature on the paraneoplastic neurological syndromes in breast cancer is also included.

Hemifacial spasm (HFS) is a movement disorder characterised by involuntary paroxysmal facial movements that usually involve the orbicularis oculi and then spread to the other facial muscles. A microvascular compression and demyelination of the seventh nerve at its exit from the brain stem is considered to be the main aetiology of HFS. In addition to rare idiopathic (cryptogenetic) cases, others causes of HFS exist: tumours or vascular malformations have been described, of both the ipsilateral and contralateral cerebellopontine angle (CPA). However, space-occupying lesions in locations other than CPA are usually not thought to be responsible for HFS. Here we describe the case of a 45-year-old woman suffering from HFS, who dramatically improved after surgical removal of a tentorial paramedian meningioma.

There are few reports about drug-related effects on PD pregnancy. We describe the case of a woman affected by PD treated with pramipexole monotherapy during pregnancy. The child, born by caesarean delivery, is healthy, whereas motor disability of the mother progressively increased to the point that levodopa therapy was necessary.

Presenilin 1 and 2 are 2 highly homologous genes involved in familial Alzheimer disease. While more than 100 mutations in presenilin 1 are known to segregate with the disease in familial Alzheimer disease, only 9 mutations of presenilin 2 have been identified to date. We report the clinical and neuropathological phenotype of FLO10, the large Italian Alzheimer kindred associated with methionine to valine substitution at residue 239 of presenilin 2. The patients showed a remarkable variability in age of onset of symptoms, disease duration, and clinical presentation. The neuropathological study of 2 patients revealed peculiar features in addition to neurofibrillary changes and A beta amyloid deposits in the neuropil and vessel wall. Ectopic neurons in the subcortical white matter, often containing neurofibrillary tangles, were found in both patients, one of whom presented with epilepsy. Furthermore, 1 patient showed an unusually high number of ghost tangles in the cerebral cortex. These observations indicate that the Alzheimer kindred FLO10 associated with M239V mutation of presenilin 2 is characterized by some peculiarities of the clinical and neuropathologic phenotype compared to sporadic Alzheimer disease.

We describe a patient with ophthalmoplegic migraine and left sixth nerve palsy, in whom disease's onset occurred at middle age.

Butoctamide hydrogen succinate (BAHS) has been proved to increase REM sleep in patients with reduced REM sleep. Following previous experiments on the effects of BAHS on nocturnal sleep of mentally retarded (MR) subjects, a polygraphic study was conducted on 20 MR subjects (age 8-14 years) to verify the effects of BAHS, 1) after long-term administration and 2) in different etiologies of MR. Subjects were divided into two balanced groups receiving placebo or 400 mg BAHS before sleep for a 6-month period. Basal sleep did not differ substantially in the two groups, both presenting reduced REM sleep. Low amounts of REM sleep were partially reversed by BAHS administration, which caused a significant increase in the REM sleep stage. Post-treatment sleep modifications found in the experimental group were not observed in the control group. BAHS produced its effects on REM sleep immediately after the first administration of the drug, but they became more apparent after long-term treatment. Our findings indicate that long-term administration of BAHS at low dosage maintains its effects on REM sleep of mentally retarded children, causing modifications similar to those previously obtained with single administration at higher dosages in cats, in healthy young and elderly volunteers and in Down's syndrome children. In addition, our observations demonstrate the effectiveness of BAHS on REM sleep, when utilized in mental retardation of etiologies other than Down's syndrome.

This paper describes EEG and clinical findings resulting from a follow-up investigation in a group of 18 males with fragile X syndrome, in whom a characteristic paroxysmal EEG pattern was previously described. The following types of evolution were observed: (1) disappearance of the pattern (with a gradual lowering of the amplitude of spikes and in some cases with asynchrony between the two hemispheres); (2) disappearance of the quasi-rhythmic centrotemporal spikes and persistence of bisynchronous polyspike and wave complexes in the temporo-parieto-frontal regions; and (3) persistence of the previously observed pattern. These results confirm the already observed similarity between this condition and the benign childhood epilepsy with centrotemporal spikes, also from the maturational point of view; on the other hand, they also indicate some difference (i.e., mental retardation, slow background EEG activity, brain atrophy). Moreover, these findings are encouraging for the possible development of research in the field of molecular genetics in epilepsy, because they provide a precise site of investigation on the X chromosome.

We report on the incidence of seizures in 113 patients with Down Syndrome (DS), 43 coming from the OASI Institute for Research on Mental Retardation and Brain Aging, Troina, and 70 from the outpatient clinic of the Department of Pediatrics, University of Catania. We obtained the following results: 15 (13.2%) patients had seizures; 6 (5.3%) febrile seizures (FS) and 9 (7.9%) afebrile seizures (aFS). Among the latter group 2 patients had generalized tonic-clonic seizures, 3 partial complex seizures, and 4 infantile spasms. The seizures appeared early in life. Only 2 adult patients had seizures. These results suggest that patients with DS show a higher incidence of FS and of aFS than non-DS individuals. Seizures in DS may be an epiphenomenon of the neurological abnormalities, both anatomical and functional, usually observed in these patients.

It has previously been demonstrated that both Myelin Basic Protein (MBP) and S-100 are released in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during acute phases of exacerbation of the disease. In order to investigate the pathobiological significance of the release of these two proteins into the CSF, MBP and S-100 were assayed in 10 MS patients during the five weeks following onset of an acute exacerbation. MBP was detectable in CSF during the first three weeks after exacerbation, while S-100 was detectable during the entire period of observation, at least in some of the patients. MBP reached its highest CSF concentrations during the first two weeks while S-100 did so in the third week, decreasing thereafter. This difference in time of presence of MBP and S-100 in the CSF is probably due to the different biological origin, MBP being a marker of myelin sheath injury, and S-100, more probably, of astrocytic activity.

The authors describe a case where a parkinsonian symptomatology is associated with pneumoencephalographic and RISA-cisternographic findings typical of an occult normal pressure hydrocephalus. They discuss their personal contribution in the light of what has been already reported in the literature on the same subject. They conclude that a CSF dynamics disturbance among the possible physiopathogenetic mechanisms of an extrapyramidal syndrome in young subjects should be considered. On the other hand, they also emphasize the possibility that the occult normal pressure hydrocephalus may have syndromical expression which are different from the typical one initially described.

Several investigators have described the altered sleep patterns in Down's syndrome subjects. The most relevant findings have been a reduction in percentage of REM sleep, a prolonged latency to the first REM episode, an increase in undifferentiated sleep, and a reduced ratio of the oculomotor frequencies. Because it is of interest to identify new drugs able to increase the percentage of REM sleep in mentally retarded subjects, we studied the effects of butoctamide hydrogen succinate (BAHS) on nocturnal sleep in eight young institutionalized Down's syndrome subjects. BAHS produced a significant increase in the percentage of REM sleep as well as a decrease in undifferentiated sleep and latency to the first REM.

In this paper, we describe a study aiming at establishing the prevalence, specificity, and the sensitivity of a characteristic sleep EEG pattern in patients with Martin-Bell syndrome, in comparison with a sample of etiologically different mentally retarded patients. The estimation of the prevalence (11% among the total sample), the specificity, and the sensitivity, allows us to propose this pattern as an important "marker", useful in the diagnosis of the Martin-Bell syndrome.

This paper reports on the clinical, neurophysiologiccd and neuroradiological characteristics of a patient with Down syndrome unusually associated with tuberous sclerosis. In particular, epilepsy is investigated in detail and its polygraphic study and etiopathological factors are discussed. The most interesting findings are those related to the presence of a structural abnormality of the rolandic-parietal cortex, bilaterally, in the form of pachygyria.