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Contains fulltext : 88123.pdf (Publisher’s version ) (Closed access) In patients with relapsing remitting multiple sclerosis (RRMS), the effect of interferon-beta (INFb) on health-related quality of life (HR-QoL) is not firmly documented. The objective of this study is to assess HR-QoL during 2 years of treatment with intramuscular INFb and its correlation with disability. In 36 neurological practices in the Netherlands (17), Belgium (16), United Kingdom (2) and Luxemburg (1), 284 RRMS patients were treated with intramuscular INFb-1a. Physical and mental domains of HR-QoL were measured by the MS54 Quality of Life (MS54QoL) questionnaire, and disability was assessed by the Multiple Sclerosis Functional Composite (MSFC) (Timed 25-Foot Walk Test [Timed 25-FWT], 9 Hole Peg Test [9-HPT], Paced Auditory Serial Addition Test [PASAT]) at baseline and at months 3, 6, 12, 18 and 24. Expanded Disability Status Scale (EDSS) score was assessed at baseline and month 24. Pearson's correlation coefficients were determined and predefined factors were analyzed for relation to HR-QoL after baseline by stepwise regression analyses on physical and mental scores. 204 patients (71.8%) completed 2 years of treatment. Mean values for MS54QoL increased from 56.6 to 61.0 for physical (p < 0.05) and from 57.2 to 61.1 for mental domain (p = 0.07). Correlations between physical domain and MSFC was -0.40 (p < 0.05), and between mental domain and MSFC -0.24 (p < 0.05). MSFC and EDSS did not change. Increase of physical MS54QoL was associated with lower age, lower EDSS, less time for Timed 25-FWT, and higher PASAT score at baseline. Increase of mental MS54QoL was associated with higher PASAT and lower EDSS. Patients who discontinued INFb had lower physical or mental HR-QoL at baseline. In RRMS patients, 2 years of treatment with intramuscular INFb-1a is associated with an increase in HR-QoL, especially in younger patients with low disability. 01 april 2010

We report on a neuropathological analysis of two cases of TSP/HAM originating from Brazil. These two cases had, respectively, an evolution of 13 and 40 years. The main neuropathological findings consisted of spinal cord atrophy, mainly the lower thoracic cord, diffuse degeneration of the white and grey matter, rare foci of mononuclear and perivascular cuffs, and hyaline hardening of arteriolae. The supraspinal structures were normal, excepting for a slight gliosis in the cerebellum. An analysis on the long evolutive cases as described in the literature is outlined in this study. Relatamos a análise neuropatológica de dois casos de PET/MAH originários do Brasil. Estes dois casos tinham, respectivamente, uma evolução de 13 e 40 anos. O principais achados neuropatológicos consistiam de atrofia da medula espinhal, principalmente da medula torácica baixa, degeneração difusa das substâncias branca e cinzenta, raros focos de infiltrado mononuclear e perivascular, e endurecimento hialínico das arteriolae. As estruturas supra-espinhais eram normais, exceto por uma ligeira gliose do cerebelo. Uma análise dos casos de longa evolução descritos na literatura é salientada neste estudo.

We reviewed the historical, clinical and etiological aspects of the progressive chronic spastic myelopathies of unknown etiology, disserting on the clinical similarities between HTLV-I seropositive and seronegative tropical spastic paraparesis (TSP), as well as focusing on the PCR studies of the seronegative TSP.

A type-specific serological survey among 1042 random nonneurological outpatients in two cities in the state of Ceara (northeastern Brazil) shows a low prevalence of HTLV-I (0.34% in Fortaleza; 0.44% in Crato) and of HTLV-II (0.34% in Fortaleza; 0% in Crato). Among 62 chronic myelopathic patients seen in Fortaleza 27 patients were found with clinical features of tropical spastic paraparesis (TSP); 10 of 27 were found HTLV-I seropositive (37%; 95% confidence limits, 19-58%). Proviral genome detection by polymerase chain reaction in 5 seropositive and 12 seronegative patients confirmed the serological findings. This excludes HTLV-I or -II infection as a cause in the seronegative TSP patients. The HTLV-positive and -negative patients did not differ clinically and by history, except that seropositives had a longer mean disease duration, a female predominance, and a higher proportion of white Caucasians. In this population with low HTLV-I and HTLV-II prevalences, HTLV-negative TSP is at least as frequent as the HTLV-I-associated TSP.

A substrate conversion assay was used to detect gelatinase activity in the cerebrospinal fluid (CSF) of patients with various neurological disorders. Two main forms of gelatinase with an apparent molecular mass of 65 and 85 kDa, respectively, could be discerned. The high molecular mass gelatinase was detectable only in samples of patients with multiple sclerosis or other inflammatory neurological disorders. A statistically significant correlation was found between the level of the 85-kDa gelatinase and the CSF cytosis. This protease could play a role in the process of demyelination and breakdown of the blood-brain barrier in certain neurological disorders, such as multiple sclerosis.

After the first description of TSP/HAM in 1985 and the elaboration of WHO's diagnostic criteria in 1988, the experience of the professionals in this field has increased so that a critical reappraisal of these diagnostic guidelines was considered timely. Brazilian neurologists and observers from other countries met recently to discuss and propose a modified model for diagnosing TSP/HAM with levels of ascertainment as definite, probable, and possible, according to myelopathic symptoms, serological findings, and/or detection of HTLV-I DNA and exclusion of other disorders.

Objectives: (1) To determine the prevalence of swallowing problems in MS patients and its relation to the overall disability. (2) To define the most frequent symptoms suggestive of dysphagia. (3) To describe the abnormalities on manofluoroscopy (MFS). Methods: Three hundred and eight consecutive MS patients were asked whether they ever had swallowing problems. If so the questionnaire of the Johns Hopkins Swallowing Centre was applied to qualify the dysphagia. A MFS was performed in 30 patients with dysphagia covering the entire spectrum of MS. Overall disability was assessed using the Expanded Disability Status Scale (EDSS). Results: Seventy-three of our 309 patients had permanent dysphagia (24%). Another 5% had a history of transitory swallowing problems only. Permanent dysphagia started to be a problem in mildly impaired patients (EDSS 2–3). Prevalence increased together with rising disability to reach 65% in the most severely disabled subjects (EDSS 8–9). Two alarming symptoms of patients with swallowing problems, coughing or choking during the meal and a history of pneumonia were present in 59%, respectively, 12% of these patients. MFS showed deficiency of the oral phase in all patients, while only the patients with an EDSS higher than 7.5 showed abnormalities of the pharyngeal phase. Conclusions: Permanent dysphagia may already develop in mildly impaired MS patients but becomes a rather frequent finding in MS patients with moderate or severe disability. MFS is a sensitive and useful ancillary examination. Important qualitative changes of the pharyngeal phase on MFS are seen in patients with an EDSS higher than 7.5.

A case of HTLV-1 associated tropical spastic paraparesis is described in a Belgian nun who had been working as a midwife in Central Africa. Occupational exposure was the only risk factor identified. Among 2,482 Belgian expatriates in tropical countries, 92% of whom had resided in sub-Saharan Africa for an average of 15.5 years, only one Belgian-born man was found seropositive for HTLV-1. He was married to an African woman and living in Central Africa for 23 years. The risk of HTLV-1 infection is low in Belgian expatriates and on its own does not support generalised anti-HTLV screening in autochthonous Belgian blood donors.

Gosselink R, Kovacs L, Ketelaer P, Carton H, Decramer M. Respiratory muscle weakness and respiratory muscle training in severely disabled multiple sclerosis patients. Arch Phys Med Rehabil 2000;81:747-51. Objective: To evaluate the contribution of respiratory muscle weakness (part 1) and respiratory muscle training (part 2) to pulmonary function, cough efficacy, and functional status in patients with advanced multiple sclerosis (MS). Design: Survey (part 1) and randomized controlled trial (part 2). Setting: Rehabilitation center for MS. Patients: Twenty-eight bedridden or wheelchair-bound MS patients (part 1); 18 patients were randomly assigned to a training group ( n = 9) or a control group ( n = 9) (part 2). Intervention: The training group (part 2) performed three series of 15 contractions against an expiratory resistance (60% maximum expiratory pressure [PEmax]) two times a day, whereas the control group performed breathing exercises to enhance maximal inspirations. Main Outcome Measures: Forced vital capacity (FVC), inspiratory and expiratory muscle strength (PImax and PEmax), neck flexion force (NFF), cough efficacy by means of the Pulmonary Index (PI), and functional status by means of the Extended Disability Status Scale (EDSS). Results: Part 1 revealed a significantly reduced FVC (43% ± 26% predicted), PEmax (18% ± 8% predicted), and PImax (27% ± 11% predicted), whereas NFF was only mildly reduced (93% ± 26% predicted). The PI (median score, 10) and EDSS (median score, 8.5) were severely reduced. PEmax was significantly correlated to FVC, EDSS, and PI ( r =.77, −.79, and −.47, respectively). In stepwise multiple regression analysis, PEmax was the only factor contributing to the explained variance in FVC ( R 2 =.60), whereas body weight ( R 2 =.41) was the only factor for the PI. In part 2, changes in PImax and PEmax tended to be higher in the training group ( p =.06 and p =.07, respectively). The PI was significantly improved after 3 months of training compared with the control group ( p Conclusions: Expiratory muscle strength was significantly reduced and related to FVC, cough efficacy, and functional status. Expiratory muscle training tended to enhance inspiratory and expiratory muscle strength. In addition, subjectively and objectively rated cough efficacy improved significantly and lasted for 3 months after training cessation. © 2000 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Interleukin 6 (IL6) is one of the major inflammation-associated cytokines. Elevated serum or tissue levels of IL 6 have been reported to occur in several human diseases, including infections of the central nervous system (CNS), but not in non-infectious CNS inflammation, e.g. multiple sclerosis. While studying experimental autoimmune encephalomyelitis (EAE) as an animal model for autoimmune inflammation of the CNS, we found increased IL 6 levels in the CNS of mice suffering from a lethal form of the disease. IL 6 levels in the spleens and sera were not significantly increased. These findings are indicative of local production of IL6 in the CNS during EAE, and represent the first demonstration of IL6 production in non-infectious CNS inflammatory disease.

Objectives—To assess the utilisation of medical services and social (community) assistance in patients with multiple sclerosis of diVerent disability and to calculate the direct healthcare costs to society. Methods—(1) One hundred and eighty four patients with multiple sclerosis were classified into four grades of disability according to a simplified Kurzke disability status scale. (2) Patients were interviewed with a structured questionnaire containing questions on their sociodemographic status, the use of inpatient and outpatient medical services and pharmaceutical products during the previous year, the use of social assistance, and the purchase of prosthetics and charges for house adaptations during the previous five years. (3) Data were also prospectively collected by means of four week diary annotations of all medical and social acts and their duration. Results—After correction for the disability distribution the yearly costs for the 5500 patients with multiple sclerosis in Flanders was estimated to be ECU 13 106 000 for ambulatory care including rehabilitation and district nursing and ECU 3 234 000 for pharmaceutical products. To these direct medical costs ECU 3 491 000 for social assistance and ECU 4 938 000 for prosthetics and adaptations should be added. The yearly costs for admissions to hospital including permanent residence in an institution and pharmacy was ECU 26 581 000 . Home nursing and long term or permanent residence in an institution of the most severely disabled, 17% of the multiple sclerosis population, are responsible for 50% of the total direct healthcare costs and care for the 6.5% institutionalised patients accounts for 23%. Direct costs for medical care and social assistance for patients with multiple sclerosis, who account for about 0.1 % of the total population, amounts to 1% of the total healthcare budget in Flanders. Conclusion—This information on utilisation of medical services and social assistance can be used for good healthcare planning and cost eVectiveness studies. (J Neurol Neurosurg Psychiatry 1998;64:444‐450)

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficaceous protease inhibitors than those used in the combination therapy described here.

Objectives - To calculate age adjusted risks for multiple sclerosis in relatives of Flemish patients with multiple sclerosis. Methods - Lifetime risks were calculated using the maximum likelihood approach. Results - Vital information was obtained on 674 probands with multiple sclerosis in Flanders and a total of their 26 225 first, second, and third degree relatives. Full medical information to allow documentation of multiple sclerosis status was available for 21 351 (81.4%) relatives. The age adjusted risk for parents was 1.61 (SEM 0.35)%, for siblings 2.10 (SE 0.36)%, and for children 1.71 (SEM 0.70)%. For aunts and uncles, the risk was 0.66 (SEM 0.13)%. Conclusions - The risk for first degree relatives of patients with multiple sclerosis in Flanders is increased 10-fold to 12-fold; for second degree relatives, it is increased threefold. This information can be used for risk counselling in families and provides additional support for the role of more than one locus contributing to the susceptibility of multiple sclerosis.

In a retrospective study of 72 patients with developmental venous anomalies (DVA) diagnosed by MRI and/or angiography, 33 associated lesions were found in 32 patients (44%). Study of the clinical files allowed classification of the patient population into three groups. In group 1 (11 patients: 34%) the symptoms were attributed with certainty to the associated lesions (1 brain infarction, 2 multiple sclerosis patients, 1 case of meningitis, and 7 patients with tumors). In group 2 (9 patients: 28%) the symptoms were probably caused by the associated lesion and not by the associated DVA (1 contusion, 1 Sturge-Weber angiomatosis, and 7 hemorrhagic DVA). In group 3 (12 patients: 38%) the symptoms were nonspecific (10 cavernous angiomas, 1 varix with sinus pericranii, and 1 ectasia of the middle cerebral artery. These findings sustain the theory that DVA is a congenital anomaly of the venous drainage of the brain, without pathological significance, and must be considered as an incidental finding.

We demonstrate focal leptomeningeal enhancement along the chiasm on MRI in a 28-year-old man presenting with blurred vision and bitemporal visual field defects. The diagnosis of clinically definite multiple sclerosis was confirmed by laboratory investigations and brain MR findings.

We studied 200 female patients with multiple sclerosis (MS) to investigate whether pregnancy after the onset of disease influences long term disability. As an index of progression, we used the time between disease onset and wheelchair dependence. Patients who had at least one pregnancy after onset were wheelchair dependent after 18.6 years, versus 12.5 years for the other women (P < 0.0001). This difference remains statistically significant after correction for age at onset of disease.

The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoencephalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss.

In a combined retrospective and prospective study, we tried to define the prevalence of antinuclear antibodies (ANA) and its clinical relevance in neurological patients. Three hundred twenty-seven neurological patients who had ANA determined because of suspicion of connective tissue disease (CTD), were retrospectively studied. Thirty (9.2%) were ANA positive, 20 (66%) of whom had CTD. Of 327 consecutively admitted patients, prospectively studied, 18 (5.5%) were ANA positive, 5 (28%) of whom had evidence of CTD. Systemic lupus erythematosus (SLE) was the most frequently diagnosed CTD. In a prospective study of 48 multiple sclerosis (MS) patients, only 1 had detectable ANA at a dilution of 1:40. Lupus anticoagulant (LA) was prospectively detected in 2 patients but was not associated with a vascular or autoimmune systemic disease.

The MR findings in an adult patient with globoid cell leucodystrophy (GLD) or Krabbe's disease are presented. MRI showed a bilateral periventricular hyperintensity of the parieto-occipital white matter on the T2-weighted images. A hyperintense signal was seen bilaterally along the corticospinal tract. There was no immediate nor delayed contrast enhancement. The MR findings in this case of GLD are rather atypical.

Eleven patients with a relapsing-remitting form of multiple sclerosis (MS) were examined clinically and with magnetic resonance imaging scans 3 weeks before, at the day of vaccination with killed influenza virus and 3 weeks afterwards. No exacerbations were noted in the pre- or postvaccination period. Eight contrast-enhanced or active lesions were present at the onset of the study. Three new active lesions appeared at the end of the prevacci-nation period while only 1 new active lesion was found at the end of the postvaccination period. We conclude that vaccination with killed influenza virus has no clinical or subclinical short-term effect on the activity of MS.

We present a patient with adult-onset globoid cell leukodystrophy (GBL) who had almost complete deficiency of galactosylceramide beta-galactosidase. A brother of the index patient deteriorated neurologically and died at the age of 4, probably from the late-infantile form of the disease. In this family, two clinical types of GBL are probably different expressions of an identical genotype.

Epidemiological findings of twenty sporadic cases of epidemic spastic paraparesis (buka-buka) in three areas of Bandundu (Zaire) are reported. These findings suggest the involvement of an infectious agent and do not support the hypothesis of a dietary cyanide intoxication, which has been advanced to explain the outbreak of a very similar disease (Mantakassa) in Mozambique.

The authors present a case report of early onset myophosphorylase deficiency (Mc Ardle's disease) with absence of myophosphorylase protein on SDS-electrophoresis. The different varieties of myophosphorylase deficiency and the clinical investigations which may lead to the diagnosis are reviewed. In particular, the relevance and possible dangers of an ischemic forearm exercise test and the suggestion of using a needle biopsy as a preliminary screening in similar cases of metabolic myopathies are discussed.

Morphometric analysis of the innervation pattern of the stromal layer of the urinary bladder was done on biopsies from 88 patients with definite multiple sclerosis (MS). The biopsies were stained for acetylcholinesterase and for S100 protein, and a semiquantitative score was assigned. Nearly 30% of the samples showed increased immunoreactivity for S100, indicating Schwann cell hyperplasia. In 16% a decreased S100 immunoreactivity was found, the significance of which is unclear. More than 90% had normal acetylcholinesterase activity. No correlation could be demonstrated for age, sex, severity and duration of the disease, the presence of cystitis and type of detrusor dysfunction. The finding of altered S100 immunoreactivity in MS bladders could indicate that MS also affects the peripheral nervous system and is not limited to the central nervous system as classically described. This finding warrants further investigations.

In a search for early prognostic features in multiple sclerosis, the progression rate was calculated in 200 consecutive multiple sclerosis patients who had had a lumbar puncture, and correlated with age at onset, type of disease course, the patient's sex, as well as with indices of blood-brain barrier breakdown and intrathecal IgG synthesis. The present study demonstrates that age at onset plays a role in determining whether the disease will be remitting-relapsing or chronic progressive. Age at onset is also a factor determining the rate of progression of the remitting-relapsing form, but is without influence on the progression of the chronic progressive form. A chronic progressive disease course per se (independent of age at onset) is also associated with a more rapid deterioration. The patient's sex does not appear to be a differentiating factor. Only inconsistent correlations were found between IgG index or number of oligoclonal bands in the CSF and disease progression.

Summary Hypothermia, defined as a core temperature less than 35°C has multiple causes and several neurological consequences. The cases of three patients with definite multiple sclerosis since more than a decade are reported, who presented with several episodes of coma and hypothermia. Systematic neuropathologic examination of the hypothalamus in one case did not reveal any abnormality.

The Dutch version of the McGill Pain Questionnaire was composed mainly by following R. Melzack's methodological design. The recommendations of the Finnish research team were considered and integrated. In the first phase as wide an inventory of pain descriptions as possible was drawn up. In the second phase, these pain descriptions were categorized by pain experts and students according to quality aspects. In the third phase the pain descriptions were judged according to intensity aspect as well by pain experts, by students and by pain patients. Finally a fourth phase was set up to obtain insight into the reliability and validity of the McGill Pain Questionnaire - Dutch Version (MPQ-DV).

Two brothers developed a neurological condition characterized by homochrony and homotypy: the first symptoms in both were generalized epileptic seizures, occurring at about the same age (30 years in the elder, 32 years in the younger), followed by a cerebellar syndrome with myoclonic jerks and some extrapyramidal symptoms. The elder of the two boys died at the age of 33 years. Histology showed extensive storage of ceroid-lipofuscin in the central nervous system (curvilinear bodies), in hepatocytes, in heart muscle and in the retina. In the younger boy, still living, a muscle biopsy (peroneal muscle) revealed accumulation of membrane-bound osmiophilic inclusions with curvilinear profiles. Retinal storage in Kufs' disease has never been documented. Muscle biopsy as a diagnostic tool for Kufs' disease has not been reported.

SummaryA Belgian airline pilot had paraplegic poliomyelitis in 1986, after infection in Dakar (Senegal) with wild-type poliovirus 1 which was isolated from his stools 6 weeks after onset. Serology available from day 25 showed the concomitant rise of type 2, but no longer of type 1 antibodies.Exercise to fight off early symptoms probably aggravated severity; residual sequelae are serious. The patient had probably never been vaccinated. The case stresses the need for (re) vaccination of travellers to endemic areas. For this purpose, there is now a choice between live oral and killed injectable polio vaccines.

The effect of short-term intensive cyclophosphamide therapy upon 21 patients with moderately advanced multiple sclerosis is compared with a non-treated control group of 21 patients retrospectively matched for global disability. The progression of the disease was evaluated by regular disability scoring, and the results were analyzed by non-parametric statistical tests. No significant differences in the progression of the disability could be detected during a follow-up period of 2 years.

Utilizing fluorescein-conjugated monoclonal antibodies and flow cytometry, lymphocyte subsets in cerebrospinal fluid (CSF) and blood from 25 active neurologic disease patients, and in blood from 21 healthy donors were evaluated. CSF showed increased percentages of the T-helper/inducer (TH) and decreased percentages of the T suppressor/cytotoxic (TSC) subsets, as well as increased ratios of TH/TSC compared with paired or normal blood values. CSFs with increased cell counts had significantly higher levels of T total and TH subsets than those with baseline counts, but no differences were observed in levels of TSC or HLA-DR (+) subsets. Of particular significance, both the CSF and blood of neurologic disease patients (but not blood of healthy donors) demonstrated increased TH/TSC ratios as the % of total T-cells increased. The increase in total T cells was due almost entirely to increases in the TH subset, while the TSC subset remained nearly constant. Taken together these data suggest that increased levels of the TH subset in neurologic disease patients anticipates a selective migration of these cells into the CSF, resulting in altered TH/TSC ratios and escape from regulation by T-suppressor cells.

A 21 year old female patient developed Sudeck's atrophy of the right foot secondary to a chronic Achilles tendinitis. The condition was complicated by the occurrence of painful muscle spasms in the right leg and incontinence of urine. The spasms had characteristics of both a tonic ambulatory foot response and a spinal flexor reflex. The movements disappeared during sleep. Regional anaesthesia of the right leg made the spasms disappear both in and outside the region of anaesthesia. Backaveraging of the EEG showed the involuntary spasms to be preceded by a cortical potential similar to a readiness potential, indicating a cortical potential similar to a readiness potential, indicating a cortical component in the pathophysiology of the muscle spasms complicating Sudeck's atrophy.

The HLA-A, -B, -C and -D were determined in 200 multiple sclerosis (MS) patients, 64 of whom underwent a CSF examination. Their frequencies were correlated with the rate of disease progression and with factors thought to influence disease progression, including onset age, type of clinical course and intrathecal IgG synthesis. No correlation was found between HLA haplotypes and progression rate or type of disease course. Patients starting MS after age 31 years carried the DR2 determinant more frequently (P = 0.016) than patients with onset before this median age. Although the greatest proportion of patients with an IgG index greater than 1.5 or more than 15 oligoclonal bands in their CSF were DR2 carriers, no statistical difference was found in the intrathecal IgG synthesis of HLA-DR2 (+) and (-) patients.

We have confirmed that the electrical stimulation of the splanchnic nerve in the rabbit causes glycogenolysis m a cyclic AMP-independent way as found by Shimazu and Amakawa [1]; glycogen phosphorylase (1,4-α- d -Glucan: orthophosphate α-glucosyltransferase, EC 2.4.1.1) was activated, but phosphorylase b kinase (ATP: phosphorylase b phosphotransferase, EC 2.7.1.38) was not. We could, however, not confirm the observation of a decrease in phosphorylase phosphatase (phosphorylase a phosphohydrolase, EC 3.1.3.17) activity. Pretreatment of the rabbits with the α-adrenergic blocking agent phentolamine prevented the splanchnic nerve stimulation from activating glycogen phosphorylase. The addition of norepinephrine (10 −7 M) to isolated rabbit hepatocytes activated glycogen phosphorylase without an activation of phosphorylase b kinase. At 10 −6 M, norepinephrine activated both enzymes. Phentolamine blocked the activation of glycogen phosphorylase by norepinephrine at 10 −7 M but not at 10 −6 M. Absence of Ca 2+ from the incubation medium prevented norepinephrine (10 −7 M) from activating glycogen phosphorylase. The ionophore A 23187 also caused an activation of phosphorylase (but not of phosphorylase b kinase) provided that Ca 2+ was present in the incubation medium. These data indicate that sympathetic nervous control of liver glycogenolysis is achieved, via α-adrenergic receptors, by an increased concentration of cytosolic Ca 2+ ions which stimulate rather than activate phosphorylase b kinase. The neurotransmitter involved is most probably norepinephrine.

Several clinical trials with transfer factor (TF)1–3 carried out in the 1970s, showed no beneficial effect on multiple sclerosis (MS) patients.

• Among the hereditary affections of the nervous system associated with deafness, a rare condition called "progressive pontobulbar palsy with deafness" has been described. In this slowly progressive condition, hearing loss and vestibular areflexia are almost always the first symptoms, occurring in late childhood or early adulthood. Only 18 cases—some sporadic, several familial—have been published without a full report of pathological findings. The clinical and pathological data of two new cases—one familial, one sporadic—are described here. There are differences from other forms of bulbar paralysis, lower motor neuron diseases, and some spinocerebellar hereditary affections. In view of the homochrony and homotypy in familial cases and the pathological findings, progressive pontobulbar palsy with deafness appears to be an abiotrophic process with autosomal recessive inheritance.

Multiple sclerosis (MS) and Leber's hereditary optic neuropathy (LHON) have been found to occur in combination. Based on an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS. All three primary LHON mutations occurring in the European and North American populations have been found to be associated with an MS-like syndrome. The neurological characteristics of MS associated with LHON are indistinguishable from those of MS in general, but the severe and bilateral visual symptoms and signs justify considering these patients as a clinical subgroup of MS and screening them for LHON mutations. However, screening LHON patients for MS appears to be more rewarding.

One hundred five patients with MS were divided into three groups matched for age, sex, and disability, and treated with either placebo, transfer factor prepared from leukocytes of random donors, or transfer factor from leukocytes of family members living with the patients. There were no differences in the three treatment groups for changes in disability, activities of daily living, or evoked potentials. Eighteen months of transfer factor therapy had no effect on gamma-interferon production or natural killer cell activities.