Unbalanced Peptidergic Inhibition in Superficial Neocortex Underlies Spike and Wave Seizure Activity.

Slow spike and wave discharges (0.5-4 Hz) are a feature of many epilepsies. They are linked to pathology of the thalamocortical axis and a thalamic mechanism has been elegantly described. Here we present evidence for a separate generator in local circuits of associational areas of neocortex manifest from a background, sleep-associated delta rhythm in rat. Loss of tonic neuromodulatory excitation, mediated by nicotinic acetylcholine or serotonin (5HT3A) receptors, of 5HT3-immunopositive interneurons caused an increase in amplitude and slowing of the delta rhythm until each period became the "wave" component of the spike and wave discharge. As with the normal delta rhythm, the wave of a spike and wave discharge originated in cortical layer 5. In contrast, the "spike" component of the spike and wave discharge originated from a relative failure of fast inhibition in layers 2/3-switching pyramidal cell action potential outputs from single, sparse spiking during delta rhythms to brief, intense burst spiking, phase-locked to the field spike. The mechanisms underlying this loss of superficial layer fast inhibition, and a concomitant increase in slow inhibition, appeared to be precipitated by a loss of neuropeptide Y (NPY)-mediated local circuit inhibition and a subsequent increase in vasoactive intestinal peptide (VIP)-mediated disinhibition. Blockade of NPY Y1 receptors was sufficient to generate spike and wave discharges, whereas blockade of VIP receptors almost completely abolished this form of epileptiform activity. These data suggest that aberrant, activity-dependent neuropeptide corelease can have catastrophic effects on neocortical dynamics.

Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiological polyneuropathy. There was no difference between the subgroups of patients with normal versus abnormal sensory NCS findings with respect to age, duration and region of onset. CONCLUSION: The findings support previous reports of sensory involvement in ALS, and raise the question of whether patients with ALS with sensory nerve abnormalities represent a variant of ALS. ALS associated with generalised sensory system abnormalities may be consistent with degeneration of motor neurones and dorsal root ganglion cells.

A morphological analysis of the macro motor unit potential.

The technique of macro EMG is used to investigate the motor unit architecture in a number of pathological conditions. Amplitude and area are the most commonly used criteria, but these parameters alone are not sufficient to assess the complexity of the macro MUP morphology. In an attempt to examine the morphology of the macro MUP in more detail, additional measures were investigated including, (i) average power, (ii) duration, and (iii) number of phases. Macro MUP duration was defined as the time parameter that contains a particular fraction (90%) of the total power of the potential. The above mentioned parameters were evaluated for normal subjects and for patients suffering with motor neuron disease (MND), spinal muscular atrophy (SMA), and Becker's muscular dystrophy (BMD). It is shown that high amplitude and average power macro MUPs give shorter macro MUP duration than macro MUPs with normal amplitude. In contrast, in low amplitude macro MUPs there is a tendency towards a higher duration measure, as compared with the duration of the normal amplitude macro MUPs. Also, t-test results for the duration measure gave a significant difference between the NOR-MND, and no significant difference between the NOR-BMD and NOR-SMA groups at P<0. 05. Significant difference between the NOR and the three disease groups investigated was obtained for the parameters log amplitude, log area, and log average power. The number of phases was not significantly different between the NOR and the rest of the groups. In conclusion, the average power and duration parameters can possibly be used as additional discriminators to detect abnormalities of the macro motor unit potential in both needle and surface EMG but further investigation is necessary.

Neuromuscular effects of Papuan Taipan snake venom.

Snakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single-fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.

Transrectal ultrasound guided needle electromyography of the urethral sphincter in males.

Needle electromyography (EMG) of the urethral sphincter in males is commonly performed using a transperineal approach. The technique involves transcutaneous insertion of an EMG needle into the sphincter guided by the investigator's finger placed in the rectum. We describe a new method of needle placement into the urethral sphincter in males using transrectal ultrasound (TRUS). With the patient in the left lateral position, the apex of the prostate gland is identified in the longitudinal plane. Using the TRUS biopsy channel, a specially designed long EMG needle is inserted into the sphincter commencing approximately 1.5-2 cm distal to the prostatic apex in an oblique fashion. This method allows precise identification of the site for needle insertion, reducing blind attempts at localization. The transrectal route is much less uncomfortable to patients, potentially improving patient compliance and overall effectiveness of the technique.

The clinical application of dorsal penile nerve cerebral-evoked response recording in the investigation of impotence.

OBJECTIVE: To determine whether recording of penile cerebral-evoked response (CER) is useful in the assessment of men with impotence. PATIENTS AND METHODS: A total of 280 impotent men underwent CER recording as part of an assessment for a complaint of impotence. They were categorized from findings in the history and examination as having non-neurogenic impotence (n = 106), impotence related to existing neurological disturbance (n = 67), type I diabetes (n = 49) or type II diabetes (n = 58). Increased period of latency or absence of first positive peak (P1) on CER were used as the criteria for an abnormal response with reference to an age-matched control group of potent men (n = 34). RESULTS: Overall, impotent men with diabetes or a history of neurological disturbance had significantly longer P1 latencies and lower response amplitudes compared with the control group. In contrast the CER recorded from men with non-neurogenic impotence was similar to the control group. Individual results showed an increased period of latency or absence of P1 in 100 (36%) impotent men, 72 (72%) of whom were diabetic or had a history of neurological dysfunction. CER abnormalities were associated with neurological signs on physical or cystometrographic examination in 40 (40%) individuals. CONCLUSION: Although technically satisfactory, the clinical usefulness of CER recording is limited by the poor discriminatory value of response latencies. Most abnormal results could be predicted by the presence of diabetes or pre-existing neurological dysfunction, or by evidence of neurological deficit on physical examination. The test is not therefore suitable for routine clinical assessment of impotence but may be worthwhile if objective evidence of penile sensory dysfunction is required.

KANDID--an EMG decision support system--evaluated in a European multicenter trial.

KANDID is an advanced EMG decision support system dedicated to the support of the clinical neurophysiologist during EMG examinations. It has facilities for test planning, automatized and structured data interpretation, EMG diagnosis, explanation, and reporting. In a prospective European multicenter field trial, the agreement levels between clinical neurophysiologists and KANDID's diagnostic statements were measured under ordinary clinical EMG practice. KANDID was assessed in 159 individual patient EMG examinations by nine clinical neurophysiologists at seven different EMG laboratories. The reasoning of KANDID was considered understandable for the examiners in 80-90% of cases. The agreement level for the electrophysiological states of muscles and nerves between KANDID and the individual examiners was, on average, 81%. The corresponding diagnostic agreement with KANDID was, on average, 61%. A pronounced interexaminer variation in the agreement level related to the different EMG centers was observed. All Danish and Belgian examiners agreed with KANDID in more than 50% of their cases with regard to the EMG diagnosis, while the English examiners were in agreement with KANDID in 50% or less of their cases. These differences were possibly due to differences in epidemiology, examination techniques, control material, and examination planning strategies. It is concluded that it is possible to transfer systems like KANDID out of their development sites and apply them successfully if they can be locally customized by the clinical end users via editors.

Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat.

1. A study of neuromuscular function in regenerating skeletal muscle fibres in the rat soleus muscle has been made. The muscle fibres were damaged in vivo by the injection of the myotoxic venom component notexin, and then allowed to regenerate spontaneously. 2. Regenerating muscle fibres generated action potentials and contracted following direct intracellular stimulation as early as 4 days after the injection of notexin. 3. Miniature endplate potentials (MEPPs) were recorded at a minority of synapses at 3 days, and from all synapses by 5 days. The mean amplitude of MEPPs in a given fibre was directly proportional to muscle fibre input resistance. 4. Spontaneous transmitter release in the regenerating fibres was relatively insensitive to changes in [K+]0 but the effect of Ruthenium Red on spontaneous release was similar in the regenerating and control muscle fibres. 5. Functional innervation, defined as the ability to generate an indirect action potential, was restored in 97% of fibres by 10 days. The generation of an action potential was always associated with a twitch of the muscle fibre. Those fibres that were unable to generate an action potential usually exhibited a low membrane potential (ca -50 mV). These fibres could generate action potentials if they were hyperpolarized using an intracellular current-passing microelectrode. 6. The quantal content of endplate potentials (EPPs) was estimated from the mean EPP and mean MEPP amplitudes in cut muscle fibre preparations. These estimates suggested that quantal content was low at the earliest stages of regeneration, but increased as the muscle fibres matured and became normal at 10-21 days. 7. During repetitive stimulation at 30 Hz there was a fall in the amplitude of EPPs of 40-45%. The fall was similar in regenerating and control fibres. Conducting synapses never exhibited failure to generate an EPP during the period of high-frequency stimulation.

Artificial neural nets in computer-aided macro motor unit potential classification.

The use of macro electromyography to obtain a macro motor unit potential (MMUP) is described. At least 20 potentials are measured from a single muscle to obtain a reasonable estimate of the parameters of an average motor unit potential. The MMUP data are analyzed by means of the peak-to-peak amplitude and the integral of the central 50 ms of the signal. The possibility of using artificial neural networks (ANNs) to analyze the macro data in a way that makes no assumptions about the relationships between the parameters and without recourse to conventional modeling methods is discussed. The results of an analysis carried out on 820 MMUPs recorded from 41 subjects who were classified on the basis of a clinical opinion and the appearance of a muscle biopsy are presented and discussed.

Solitary extranodal lymphoma of sciatic nerve.

A solitary extranodal malignant lymphoma (non-Hodgkin's lymphoma, centrocytic type) of the sciatic nerve is described in a 64-year-old woman. Whereas previous reports of peripheral nervous system lymphoma have described multifocal lesions and generally an association with systemic lymphomas, in this case the lymphoma was confined to a segment of a peripheral nerve and was not associated with systemic lymphoma. The clinical presentation was a progressive weakness and sensory disturbance in the right leg. Clinical and electrophysiological examination indicated a lesion in the sciatic nerve, and computerised tomography of the right thigh revealed an enlarged distal segment of the sciatic nerve. On surgical exploration, a fusiform tumour of the sciatic nerve was resected. Pathological examination, including immunohistology and electron microscopy revealed a malignant lymphoma. An unusual histological feature was the presence in the tumour and infiltrated nerve of an extracellular eosinophilic non-amyloid material, similar to that occasionally seen in nodal lymphomas. The patient showed no evidence of lymphoma at other sites at the presentation and this has been confirmed at a 9-month review.

Multiple intracranial enterogenous cysts.

The case of a 40-year-old woman with increasing ataxia is described. Although the clinical presentation and evoked response studies raised the possibility of multiple sclerosis, further investigation revealed multiple cystic intracranial lesions. Surgical excision of one of the lesions relieved the patient's symptoms. Histological examination revealed that this was an enterogenous cyst. Although single cysts of this type have rarely been reported occurring in the posterior cranial fossa, the occurrence of multiple lesions, some in the supratentorial compartment, appears to be unique.

Comparison of electrophysiological and histochemical methods for assessing the spatial distribution of muscle fibres of a motor unit within muscle.

The spatial distribution of muscle fibres of a motor unit has been examined in patients with a variety of neuromuscular disorders using the fibre density (FD) technique of single fibre EMG and the enclosed fibre count (EFC) method, and the results of the two approaches compared. Agreement between the findings occurred in 64% of cases; an increase in both parameters was seen only in neurogenic conditions. FD was found to be more sensitive to minor disturbances of motor unit architecture as seen in myopathies and mild neurogenic states, and this factor together with sampling differences accounted for most of the discrepancies between the two methods. The finding of normal FD and EFC values in the presence of fibre type disproportion helped to exclude reinnervation as the cause by confirming the predominantly diffuse distribution of muscle fibres.

Visual, cortical somatosensory and brainstem auditory evoked potentials following incidental irradiation of the rhombencephalon.

Visual, cortical somatosensory and brainstem auditory evoked potentials were recorded before incidental irradiation of the rhombencephalon and at 11 weeks and eight months after completion of treatment. No patient experienced neurological symptoms during this period. No consistent changes in evoked potentials were found. The failure to demonstrate subclinical radiation-induced demyelination suggests either that the syndrome of early-delayed radiation rhombencephalopathy occurs in an idiosyncratic manner, or that any subclinical lesions are not detectable by serial evoked potential recordings.