Adult-onset nemaline myopathy and monoclonal gammopathy: a case report.

A 47-year-old female developed proximal limb weakness after hysterectomy for uterine fibromatosis. Muscle strength slowly improved, but relapse occurred at age 52. She presented with progressive gait difficulty, proximal limb weakness, and painful calves. Family history was not contributory. Cranial nerves, deep tendon reflexes, and sensation were normal. Serum creatine kinase was normal. An IgG kappa monoclonal protein was found. Nerve conduction studies were normal, but EMG showed brief small polyphasic motor unit action potentials with early recruitment in proximal muscles. Muscle biopsy showed abundant rods, atrophic muscle fibres, and type 1 fibre predominance. The sarcolemma was immunoreactive for IgG kappa. Plasmapheresis was unsuccessful, but methylprednisolone and azathioprine led to moderate improvement of muscle strength, associated with reduced monoclonal protein levels. This is the third case report, describing the association of monoclonal gammopathy and late-onset nemaline myopathy. Presence of a monoclonal protein at the sarcolemma and responsiveness to immunosuppressive treatment are suggestive of a dys-immune origin.

Chronic demyelinating hypertrophic brachial plexus neuropathy.

A patient with unilateral, painless, chronic progressive upper limb sensorimotor deficit showed electrophysiological evidence of a focal demyelinating neuropathy with almost complete conduction block across the brachial plexus. Magnetic resonance imaging disclosed marked brachial plexus hypertrophy. Intravenous immunoglobulin led to fast and complete recovery, maintained by intermittent perfusions. Hypertrophic brachial plexus neuropathy can be a presentation of focal chronic inflammatory demyelinating polyradiculoneuropathy. Objective and quantitative assessment of hand function is useful to evaluate treatment results and to optimize treatment regimens.

Physostigmine results in an increased decrement in brain glucose consumption in Alzheimer's disease.

The responsibility of cerebral cholinergic lesions for the weak clinical response to cholinergic neurotransmission enhancement of Alzheimer's disease (AD) was studied by measuring the effects of physostigmine on glucose consumption and neuropsychological tests. Ten AD and ten aged normals (AN) were examined twice, under placebo and under maximal tolerated dose of physostigmine, in randomized order and blind fashion. Under physostigmine, both groups showed better performances in tests measuring attention (P < 0.05-0.001) but not long-term memory, and cerebral glucose consumption was regionally modified (P < 0.0001). We observed a regional decrease in AD and in AN which was larger in AD, where each patient exhibited a mean metabolic decrease. With normalized values, AD and AN showed a similar decrease in the metabolic values of prefrontal cortex and striatum (P = 0.0003). These findings suggest that cholinergic neurotransmission enhancement depresses glucose consumption and increases selective attention in similar ways in both groups, but to a larger extent in AD. This suggests that brain metabolism in AD over-responds to enhancement of cholinergic neurotransmission. The observed weak response of clinical symptomatology to anticholinesterase agents does not appear to be due to the failure to enhance the activity of the cholinergic system in AD.

Neuroleptic binding to sigma receptors: possible involvement in neuroleptic-induced acute dystonia.

Several antipsychotic drugs, belonging to various chemical classes, were compared for their affinity for the sigma, dopamine-D2, and muscarinic receptors. Many neuroleptic drugs were found to bind with high affinity to sigma 2 receptors, and the binding affinity was clearly different from that observed for dopamine-D2 receptors. The dopaminergic and muscarinic theories for the physiopathology of acute dystonia are not completely satisfactory. Since the sigma receptors were reported to play a role in the control of movement, the high affinity of some neuroleptics for these sites suggests their possible involvement in some side effects, such as drug-induced dystonia. There was a correlation between the clinical incidence of neuroleptic-induced acute dystonia and binding affinity of drugs for the sigma receptor, except for some drugs, with a lower incidence, displaying significant affinity for the cholinergic muscarinic receptor. Therefore, we conclude that the affinity for the sigma receptor might be involved in neuroleptic-induced acute dystonia, but this might be partially corrected by the intrinsic anticholinergic properties of the drug.

Encephalitis in immunocompetent patients due to herpes simplex virus type 1 or 2: determination by polymerase chain reaction and detection of intrathecal virus-specific oligoclonal antibodies.

Serum and cerebrospinal fluid (CSF) of 13 patients have been examined to confirm and precise the diagnosis of herpes simplex virus encephalitis (HSVE). By amplifying the DNA with a nested polymerase chain reaction (PCR), we could demonstrate the herpetic origin of these cases of encephalitis. DNA of HSV type 1 or type 2 was directly identified and differentiated, by the use of both type-specific primes in the same reaction. The primer sequences were chosen in the glycoprotein D region for HSV type 1, and in the glycoprotein G region for HSV type 2. Only one case was due to the latter. In all but one cases, an immunoaffinity-mediated capillary blotting study was also performed. This technique showed the occurrence of oligoclonal CSF-specific IgG bands, while the antigen-driven immunoblotting demonstrated intrathecal production of oligoclonal anti HSV antibodies. In most of the cases, repeated CSF analysis allowed us to study the sequential detection of viral DNA and of intrathecal synthesis of virus-specific IgG in relation to the clinical course. All the patients were treated with acyclovir. In one case, a relapse was clinically suspected, but the PCR remained negative.

Cholinergic neurotransmission has different effects on cerebral glucose consumption and blood flow in young normals, aged normals, and Alzheimer's disease patients.

Cerebral blood flow (CBF) and glucose consumption (GC) are both tracers of brain metabolic activity used to image the human brain in vivo. To know if both tracers reacted in the same manner when brain cholinergic neurotransmission was activated, CBF and GC were measured in young normals (YN), aged normals (AN), and Alzheimer's Disease patients (AD) using positron emission tomography (PET), H2 15O, and 18F-FDG. Each subject was studied twice, under placebo and physostigmine, in randomized order and blind fashion using the maximal tolerated dose of physostigmine individually determined. Under physostigmine CBF increased significantly (P = 0.0007) in posterior regions of the cerebral cortex and in the subcortical structures. Inversely, GC was decreased significantly in most regions. The largest decrease was seen in the prefrontal region of the cerebral cortex (P < 0.0001). Significant regional decreases were registered in all three groups of subjects, but were larger in AD than in controls. Looking at the absolute values of prefrontal cortex metabolism we found no correlation (r = 0.04) between the responses of CBF and GC. After normalization of the regional values for the mean we found a significant positive correlation between the responses of CBF and GC (r = 0.71, P < 0.0001). These findings suggest two components in the CBF response to physostigmine: one metabolic, depressive, and regional which follows the GC response; and one vascular, larger, diffuse, and opposite in direction to the metabolic component. These results have implications for the interpretation of CBF values as tracer of brain metabolic activity when brain cholinergic neurotransmission is manipulated.

Idiopathic hypereosinophilic syndrome revealed by central nervous system dysfunction.

The idiopathic hypereosinophilic syndrome (HES) is a rare disease, characterised by persistent eosinophilia (> 1500/mm3), without underlying cause, provoking multiple organ system injury. Morbidity and mortality are mostly associated with the HES cardiopathy. Neurological signs are also frequent. Neurological dysfunction can be central (encephalopathy, organic psycho-syndrome) and peripheral (polyneuropathy, mononeuropathia multiplex, autonomic neuropathy, polymyositis). The encephalopathy is not always caused by distant thrombo-embolic events originating from the HES cardiopathy. We describe a patient with idiopathic HES central nervous system dysfunction, in the absence of cardiopathy. Furthermore we briefly discuss pathophysiological aspects, treatment modalities and the prognosis of the HES, in relation to our patient.

[A case of metamorphopsia restricted to faces and different familiar objects]. / Etude d'un cas de métamorphopsie limitée aux visages et à certains objets familiers.

The case of a 19-year old patient suffering of transient metamorphopsia restricted to familiar faces and familiar objects is reported. This clinical sign resulted from a small right occipitotemporal haemorrhage due to a sub-cortical metastasis. The patient claimed that faces are distorted and look more pleasant. There were neither visual field defects nor visual agnosia. MRI revealed a small high signal area in the right fusiform gyrus. The structural and functional aspects of the metamorphopsia are documented and discussed in relation to aperceptive prosopagnosia. More specifically, it is suggested that facial metamorphopsia and aperceptive prosopagnosia express the same underlying disorder differing only in terms of severity.

Five-year experience in the treatment of focal movement disorders with low-dose Dysport botulinum toxin.

We report the results of botulinum toxin type A (Dysport, Porton Products, UK) treatment over 5 years in 107 patients with blepharospasm, Meige's syndrome, oromandibular dystonia, hemifacial spasm, cervical dystonia, and writer's cramp. Electromyography was used to localize dystonic muscles and guide Dysport injections in Meige's syndrome, oromandibular dystonia, cervical dystonia, and writer's cramp. All but 2 Meige's syndrome and 2 writer's cramp patients responded to treatment. Improvement was dramatic in blepharospasm (79%) and hemifacial spasm (90%); pronounced in cervical dystonia (74%); and moderate in Meige's syndrome (53%), oromandibular dystonia (57%), and writer's cramp (34%). Although Dysport doses were 50-75% lower than usually reported, response and improvement rates as well as relapse intervals were similar to those of others. To treat cervical dystonia relapses, only 50% of the initial dose was required for continued optimal relief of symptoms. Low-dose Dysport was associated with a very low incidence of dysphagia in cervical dystonia.

The intrathecal synthesis of virus-specific oligoclonal IgG in multiple sclerosis.

A highly sensitive antigen-mediated capillary blot technique was developed for the detection of virus-specific oligoclonal IgG in paired CSF and serum samples from patients with various neurological diseases. In multiple sclerosis, intrathecal synthesis of oligoclonal antibodies was present against measles (70%), rubella (60%), varicella zoster (40%) and mumps (30%); in most cases (75%), such synthesis involved two or more viruses. In contrast, antibodies against a non-neurotropic virus (cytomegalovirus) were rarely produced in CSF from MS patients (5%). However, this 'polyspecific' reaction was not restricted to MS samples but was also observed in neurolupus and in the late phase of infectious diseases of the central nervous system. These anti-viral antibodies could be produced without de novo replication of the corresponding viral genome and are likely mere bystanders of an ongoing immune response.

Occurrence of oligoclonal IgM bands in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study.

We developed a highly sensitive and specific immunoaffinity-mediated capillary blot technique for the detection of oligoclonal IgM bands in CSF and sera from patients with various neurological disorders. Pre-treatment of the samples by dithiothreitol was necessary to obtain a migration of the IgM molecule into the gel of isoelectric focusing. IgM was then transferred by immunoaffinity onto a polyvinylidene difluoride sheet previously coated with anti-IgM antiserum. The limit of detection was found to be 6 ng in 15-microliters samples. The presence of CSF-restricted IgM bands was considered the result of an intrathecal synthesis and was observed in 13 out of 46 (28%) patients with MS, more frequently in acute relapses (9 out of 21, 43%), including 6 cases out of 13 presenting the first bout of the disease. Similar IgM bands were also detected in 15 out of 46 (38%) patients with CNS infections, especially in cases of neurosyphilis and neuroborreliosis. The presence of CSF oligoclonal IgM bands was linked to an increase of the IgM index in the MS group, but not in the group of infectious diseases as a whole. The occurrence of CSF-restricted oligoclonal IgM bands seems to be the most specific indicator of an intrathecal synthesis of this isotype.

Sulfonylurea binding sites in normal human brain and in Parkinson's disease, progressive supranuclear palsy and Huntington's disease.

In human brain, [3H]glibenclamide binds with high affinity (KD about 3.5 nM) to sulfonylurea binding sites which are associated with ATP-sensitive potassium (KATP) channels. Regarding to the important neuromodulatory action of KATP channels in some neuronal populations, sulfonylurea binding sites were measured in several cortical areas (frontal and temporal cortex, hippocampus) and striatum (caudate nucleus and putamen) in controls and patients with Parkinson's disease or progressive supranuclear palsy. There was no modification of [3H]glibenclamide specific binding in the cerebral regions studied in both pathologies. These results indicate that KATP channels do not seem to be involved in the pathophysiology of these degenerative processes. Brain samples from five patients with Huntington's disease were studied. A small decrease in sulfonylurea binding sites was measured in the frontal cortex, caudate nucleus and putamen which could be due to the loss of either neurons or nerve endings. This low decrease contrasts with the dramatic diminution of many other markers associated with the profound striatal degeneration occurring in Huntington's disease.

Somatosensory evoked potentials and jerk-locked EEG back-averaging in myoclonic epilepsy.

Median nerve somatosensory evoked potentials (SEPs) and jerk-locked EEG back-averaging (JLA) were performed in 2 patients with left-hand myoclonus. Both SEPs were characterized by a normal parietal N20 and an enhanced N27-P27 fronto-parietal complex, but the giant central N40 described by most authors was only observed in case 1. Similarily, the aspect of JLA clearly differed in both patients. We hypothetize that both patients exhibited signs of an increased drive of the motor cortex by inputs coming from the sensory cortex. This increased drive could be mediated by the cortico-cortical connexions from areas 1-3 to area 4. In contrast, we suggest that signs of primary hyperexcitability of the motor cortex were only present in case 1, as suggested by the presence of an enhanced N40 in SEPs and the results of JLA studies.

Polyclonal and oligoclonal IgA synthesis in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study.

An intrathecal synthesis of IgA has been reported in various neurological disorders. However, the frequency of its occurrence and the electrophoretic characteristics of the locally produced IgA remained a matter of controversy. We developed a sensitive immunoaffinity-mediated capillary blot technique for the detection of polyclonal and oligoclonal IgA in the CSF of 115 patients with various neurological disorders. Paired CSF and serum samples containing 50 ng IgA after appropriate dilutions were submitted to isoelectric focusing in agarose gels; IgA was then blotted onto a polyvinylidene difluoride sheet coated by an anti-IgA antiserum or by infectious antigens. The immunoblots were revealed by an alkaline phosphatase-conjugated anti-IgA antiserum. Only five samples displayed CSF-restricted oligoclonal IgA bands, including two out of 33 from MS patients. In herpetic encephalitis (n = 5) and varicella-zoster meningitis (n = 2), a strong intrathecal production of virus-specific IgA antibodies was detectable. In such cases, faint oligoclonal IgA antibodies were superimposed on a polyclonal background. A weak local production of anti-Borrelia burgdorferi IgA antibodies was present in two out of four cases of neuroborreliosis.

Serum and CSF levels of soluble interleukin-2 receptors in MS and other neurological diseases: a reappraisal.

Soluble interleukin-2 receptors (sIL-2-R) were determined longitudinally in sera from 59 patients with multiple sclerosis (MS), from 20 patients with Guillain-Barré syndrome (GBS) and from patients with other non-inflammatory disorders of the nervous system, as well as in 147 CSF samples collected for diagnostic purposes. Significantly increased serum levels of sIL2-R were observed early in the course of GBS and in progressive (relapsing or chronic) MS, but not in patients with clinically stable MS or with an acute relapse followed by complete remission. CSF levels were high in infections of the central nervous system and in meningeal carcinomatosis, as a result of an intrathecal production, but were normal in GBS and in most (94%) MS patients.