Primary sciatic nerve lymphoma: a case report and review of the literature.

A patient with primary B cell non-Hodgkin's lymphoma of the sciatic nerve is described. He presented with neuropathic symptoms in the left leg, initially diagnosed as tarsal tunnel syndrome. Magnetic resonance imaging (MRI) identified the abnormality in the sciatic nerve. A fascicular biopsy of the sciatic nerve showed a diffuse large B cell non-Hodgkin's lymphoma. The patient was treated with chemotherapy and rituximab (anti-CD20 monoclonal antibody). Four months later he was in remission, and remains so 48 months from presentation. Primary lymphoma of single peripheral nerves may be a unique subtype of extranodal lymphoma, which usually follows an aggressive course and has a variable response to current therapeutic strategies. MRI is useful, alongside electrophysiological studies, in patients with atypical peripheral nerve symptoms.

Treatment with oral 4-aminopyridine in disorders of neuromuscular transmission.

Four patients with Eaton-Lambert syndrome, four patients with congenital myasthenia, and one patient with myasthenia gravis were treated with oral 4-aminopyridine for periods of up to 10 months, doses varying from 40 to 200 mg per day. Clinical and electrophysiologic assessment confirmed the effectiveness of the drug when given alone or in conjunction with anticholinesterases. At therapeutically effective doses, central side effects were frequent and unpredictable. Three patients had a generalized fit and one patient developed a confusional state. Adverse side effects must severely limit the place of 4-aminopyridine in the treatment of patients with these conditions.

Plasma exchange and immunosuppressive drug treatment in the Lambert-Eaton myasthenic syndrome.

We undertook serial clinical and electromyographic muscle action potential (MAP) amplitude assessments in nine patients with the Lambert-Eaton myasthenic syndrome (LEMS) over 0.5 to 2.5 years who received plasma exchange (PE; 5 to 15 exchanges over 4 to 19 days) and immunosuppressive drug (IS) treatment (prednisolone 60 to 100 mg on alternate days, azathioprine 2.5 mg/kg for 0.5 to 2.5 years), and who had no signs of carcinoma at entry. Eight patients responded to PE. The peak MAP response occurred 10 to 15 days post-PE, representing a 2.5-fold mean increase and was significant (p less than 0.01). Two of three patients who developed carcinoma responded initially to IS. Three of six noncarcinoma patients developed sustained clinical and MAP remission after 0.5 to 1 year; the three others, of whom two were intolerant of azathioprine, improved. IS and PE may benefit LEMS patients, but caution is required when carcinoma risk is high.

Response of the Lambert-Eaton myasthenic syndrome to treatment of associated small-cell lung carcinoma.

We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement.

Management and outcome of severe Guillain-Barré syndrome.

Seventy-nine patients with Guillain-Barré syndrome admitted to a neurological intensive therapy unit (ITU) between 1985 and 1992 were studied retrospectively. The mean age was 49.8 years (range 16-86) and the time between the first neurological symptom and admission to ITU was 10.2 days (0-62). Admission was precipitated by a combination of respiratory failure requiring ventilatory support (73.4%), bulbar weakness (57.0%), autonomic features (11.4%) and general medical factors (10.1%). Specific treatments included plasma exchange (65.8%), intravenous immunoglobulin (13.9%) and methylprednisolone/placebo (12.7%). Significant complications included lower respiratory tract infections (45.6%), hyponatraemia (25.3%), dysautonomia (19.0%), urinary tract infection (12.7%) and cognitive disturbances (8.9%). Four patients (5.1%) died during the acute illness. Duration of nadir correlated with duration of ventilation, duration of ITU stay and outcomes at 3 months, 6 months and 1 year. However, time to nadir, an indicator of rapidity of deterioration, did not correlate with any outcome. The low mortality in this series of acutely ill and severely disabled patients suggests that specialized intensive therapy units continue to have an important role in the management of acutely ill patients with Guillain-Barré syndrome.

Magnetic stimulation of the human brain: facilitation of motor responses by voluntary contraction of ipsilateral and contralateral muscles with additional observations on an amputee.

An intense rapidly changing magnetic field generated in a coil over the scalp can excite motor pathways to hand muscles. With a suprathreshold stimulus, the amplitude of the muscle action potential of the abductor digiti minimi is increased: by weak contraction of the muscle itself, by weak contraction of the ipsilateral first dorsal interosseus, by stronger contraction of the contralateral abductor digiti minimi, but not by contraction of the contralateral first dorsal interosseus, nor by the ipsilateral quadriceps muscle. This facilitation of response to brain stimulation may occur by two mechanisms, one related to the focussing of attention onto a particular hand, the second involving a rise in excitability of homologous motor pathways.

Excitability of the human motor cortex is enhanced during REM sleep.

A conspicuous feature of rapid eye movement (REM) sleep is atonia of postural muscles due to a powerful brainstem inhibitory effect on spinal motoneurones. However, small myoclonic jerks occur during REM sleep and increased activity of cortical neurones is suggested by the EEG. Transcranial cortical stimulation with magnetic pulses has been used to investigate motor excitability during sleep in man. Motor responses were evoked during sleep using stimuli identical to those used in wakefulness. Response amplitudes were depressed during slow wave sleep (SWS) and enhanced or the same during REM sleep. These findings suggest that the susceptibility of the human motor cortex to stimulation is enhanced during REM sleep.

Chronic asymmetrical spinal muscular atrophy.

The clinical and neurophysiological features of 18 cases of chronic asymmetrical spinal muscular atrophy are described. These were patients presenting with asymmetrical neurogenic atrophy involving one or more limbs who had no evidence of pyramidal tract dysfunction after 3 or more years of symptoms. There were twice as many males as females and the mean age of onset of the disorder was about 32 years. None of the patients had bulbar involvement. The tendon reflexes tended to be depressed. The distribution of muscle weakness in the limbs was very variable, and only slowly progressive. In 5 cases symptoms and signs were confined to the hands and forearms. Motor nerve conduction velocities to wasted muscles were slightly reduced but there was no evidence of generalised neuropathy. A diagnosis of chronic asymmetrical spinal muscular atrophy, as opposed to that of classical motor neurone disease, is favoured by an age of onset under 40 years, an absence of pyramidal signs or bulbar involvement after 3 years or more of symptoms, and depressed or absent tendon reflexes. The 2 conditions appear to be clinically distinct and prognosis is considerably better in chronic asymmetrical spinal muscular atrophy. The aetiology of this condition in unknown; it may be of relevance that 2 patients in this series had close relatives with Werdnig-Hoffmann disease.

Magnetic and electrical transcranial brain stimulation: physiological mechanisms and clinical applications.

The human brain can be stimulated by electric shocks or by brief intense magnetic fields. The latter cause only a trivial scalp sensation. Stimuli exciting the motor cortex cause contralateral muscle responses, but the threshold for excitation is markedly reduced by slight voluntary contraction of the target muscle. For small hand muscles, the overall latency from scalp to muscle is shorter by 1.8 ms when electrical stimuli are used than when stimuli are magnetic. Central motor conduction time (CMCT) can be estimated by stimulating over the scalp and then over the cervical area. In healthy subjects, the CMCT is 6.1 +/- 0.8 (SD) (n = 29). Physiological studies have shown that the facilitation of responses in hand muscles produced by voluntary contraction is also present when contralateral muscles are used, but not when a leg muscle is contracted. The mechanism of facilitation may involve neural activity at both spinal and cortical levels. Single motor units can be caused to discharge by threshold brain stimuli. These motor units are the same ones activated first during weak voluntary contractions. Clinical studies have shown that the CMCT may be greatly prolonged in patients with multiple sclerosis and that subclinical motor pathway lesions can be detected. Central conduction may also be abnormal in patients with motor neuron disease and cervical myelopathy. Side effects have not been encountered with either type of stimulator.

Magnetic stimulation of cortex: clinical applications.

Magnetic stimulation of the motor cortex is of value in the diagnosis and management of several neurological disorders. Marked latency prolongation is suggestive of demyelination of central motor pathways, whereas low-amplitude responses with little delay are more typical of disorders causing neuronal loss or axonal degeneration. Subclinical abnormalities may be demonstrated, and the technique has a potential role for quantification and monitoring of disease progress. The pattern of early electrophysiological abnormality is of prognostic value in stroke patients.

CSF protein biomarkers for proximal axonal damage improve prognostic accuracy in the acute phase of Guillain-Barré syndrome.

Early predictors of prognosis in Guillain-Barré syndrome (GBS) are needed to identify patients who are likely to make a poor recovery and to guide therapeutic decision-making in the acute phase. Here we investigate whether axonal protein biomarkers released into the cerebrospinal fluid (CSF) following proximal axonal damage improve the early prognostic accuracy in GBS. A prospective multicenter study including 132 patients (38 GBS, 38 neurological controls, 42 headaches, 14 chronic inflammatory demyelinating neuropathy). CSF levels of axonal [neurofilament (NfH) and tau] and glial (S100B and glial fibrillary acidic protein) protein biomarkers were measured on admission. Nerve conduction studies were performed at the time of lumbar puncture and patients were classified according to neurophysiological criteria. Outcome was assessed on the Hughes functional score (F-score). Poor outcome was defined as the inability to walk independently (F-score > or = 3). High NfH levels (>0.73 ng/ml) predicted poor outcome (P = 0.01) with an odds ratio of 7.3 and correlated with the outcome F-score (R = 0.51, P < 0.01), as did hTau levels (R = 0.47, P < 0.01). Patients with poor outcome had significantly higher CSF NfH (median 1.78 ng/ml) when compared to those with good outcome (0.03 ng/ml) or all of the control groups (neurological controls 0.18 ng/ml, headaches 0.06 ng/ml, chronic inflammatory demyelinating neuropathy 0.05 ng/ml). Except for age (P < 0.05) and need for ventilatory support (P < 0.05), none of the other features reliably predicted outcome. Improved prognostic accuracy in the acute phase of GBS seems possible using CSF NfH levels.

CSF neurofilament levels: a potential prognostic marker in Guillain-Barré syndrome.

Long-term morbidity from Guillain-Barré syndrome (GBS) is caused by axonal damage. This prospective study demonstrated that neurofilaments (NfHs), a biomarker for axonal damage, were of prognostic value in GBS. CSF NfH levels correlated with the F score and Medical Research Council summed score and were higher in patients with neurophysiologic evidence of axonal degeneration compared to those without. Pathologically high CSF NfH levels (>0.73 ng/mL) predicted worse motor and functional outcome.

Chronic inflammatory demyelinating polyradiculoneuropathy: MRI study of brain and spinal cord.

CNS demyelinating lesions have been reported in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). There are no studies of cord atrophy in CIDP. Ten patients with CIDP underwent brain and spinal cord MRI to investigate CNS demyelination and cord atrophy. No CNS demyelination was found, but the mean cervical cord area was significantly smaller in CIDP patients vs control subjects. Spinal cord atrophy may be related to degeneration secondary to axonal loss.

Effect of temperature on neuromuscular transmission in the Eaton-Lambert syndrome.

A patient with the Eaton-Lambert syndrome is described in whom no associated condition was discovered. There was clinical and electrical evidence that the defect in neuromuscular transmission became more severe as local temperature was raised.

Electrical stimulation over the human vertebral column: which neural elements are excited?

Supramaximal percutaneous electrical stimuli applied over the human cervical vertebral column produce maximal compound muscle action potentials (CMAPs) in abductor digiti minimi. It is important to know which neural elements are excited by these stimuli and experiments were performed to answer this question. With stimulating electrodes placed progressively lateral to the midline, submaximal CMAPs with the same latency are produced. With shocks over the cervical vertebrae in the midline, the threshold for excitation of arm muscles is much lower than for excitation of leg muscles. Comparison of conduction time from the cervical column to more distal sites on the ulnar nerve by direct measurement and by F wave latency determination shows that the latter exceeds the former by 1.6 msec. Collision experiments in which paired shocks were given at the wrist and Erb's point or the wrist and cervical column showed that recovery from blocking as interstimulus interval lengthened was similar for the two sites, and that it was possible to detect F waves from the proximal stimulus. The latency of CMAPs evoked from midline surface stimuli was identical to that from a needle stimulus near the C8 root. It is concluded that electrical stimuli applied over the cervical vertebrae in the midline excite the motor roots at their exit from the spinal canal. This finding has implications for clinical studies of pyramidal tract and proximal peripheral nerve conduction.

Neurophysiological evaluation of associated demyelinating peripheral neuropathy and multiple sclerosis: a case report.

A case of combined multiple sclerosis and demyelinating neuropathy is presented. Percutaneous electrical stimulation of the cortex and spinal cord has shown that pyramidal tract conduction time was prolonged and conduction velocity in the cord was 4 m/s. Motor conduction velocity in proximal segments of peripheral nerves was slowed to the same extent as in distal segments.

Surface EMG in the recording of fasciculations.

The usefulness of multichannel surface recording of fasciculations was evaluated by a retrospective study of 116 patients with various neurological disorders. Eight channels of a conventional electroencephalograph were used with plate electrode recordings from the upper arms and legs. Wide-spread fasciculations (defined as five or more of the eight muscle groups) were recorded in 48 of 54 patients with motor neuron disease, spinal muscular atrophy or postpolio syndrome, but noted on routine clinical examination at presentation in only 6. Eleven of 23 patients with peripheral neuropathy or myelopathy had fasciculations in five or more leads compared to one clinically, and 3 of 39 with other neurological diseases had fasciculations electrically but in only one were they clinically observed. The method is a noninvasive and sensitive adjunct to clinical examination for detecting fasciculations. Its diagnostic value is limited by the relatively high incidence of fasciculations in neuropathies and myelopathies. However, this study suggests that "false negatives" are rare and that the diagnosis of motor neuron disease should be reconsidered when less than five leads shows fasciculations.

Transcarpal motor conduction velocity in carpal tunnel syndrome.

Transcarpal motor conduction to abductor pollicis brevis (APB) was evaluated in 43 patients (70 hands) with suspected carpal tunnel syndrome (CTS). Transcarpal motor conduction was abnormal in 80% of hands compared with 11.5% with prolongated distal motor latency from wrist stimulation. Transcarpal motor conduction was comparable in sensitivity with transcarpal sensory conduction and 2nd lumbrical-interosseous latency difference. Transcarpal motor conduction is a sensitive test for diagnosis of CTS. Sensory fibers were no more susceptible than motor fibers to compression in the carpal tunnel, and fibers to APB were as susceptible as those to the 2nd lumbrical muscle.

Electrodiagnosis.

Attempts to increase the diagnostic yield and reproducibility of electrophysiological investigation of peripheral nerve disorders have led to the development of new techniques, such as measurement of nerve refractoriness, as well as the re-evaluation, refinement and modification of more conventional nerve conduction tests. Other studies have characterized the clinical and electrophysiological features of the subtypes of polyneuropathies associated with monoclonal gammopathies and have documented their natural history, providing important diagnostic and prognostic information. Techniques originating in basic neuroscience that study the excitability of neurons and nerve membranes have been applied to clinical conditions, such as motor neuron disease and cramps, and have provided considerable insight into their pathogenesis.