A Unique Constellation of Multiple Cranial Neuropathies in a Patient with Preeclampsia.

A 36-year-old nullipara at 35 weeks of gestation woke up with slurred speech and dysphagia. The next day, she developed abruption of the placenta, underwent an acute cesarean, and was diagnosed with severe preeclampsia. Neurologic examination revealed flaccid dysarthria, bilateral soft palate palsy, reduced taste of the left posterior tongue, left-sided tongue deviation, and paralysis of the left sternocleidomastoid and trapezius muscles. MRI revealed left-sided tongue edema compatible with acute left hypoglossal nerve denervation and electromyography of the left trapezius and glossal muscles showed profuse denervation potentials. In conclusion, multiple cranial neuropathies may occur in and even be a presenting symptom of preeclampsia. In this study, we report the first case of multiple cranial neuropathies involving cranial nerves IX, X, XI, and XII in a patient with preeclampsia. Possible pathogenic mechanisms of cranial neuropathy in preeclampsia include immune-mediated neuropathy with or without demyelination, microvascular thromboses, and perineural edema.

Novel Homozygous Truncating Variant Widens the Spectrum of Early-Onset Multisystemic SYNE1 Ataxia.

Pathogenic variants in the SYNE1 gene are associated with a phenotypic spectrum spanning from late-onset, slowly progressive, relatively pure ataxia to early-onset, fast progressive multisystemic disease. Since its first description in 2007 as an adult-onset ataxia in French Canadian families, subsequent identification of patients worldwide has widened the clinical spectrum and increased the number of identified pathogenic variants. We report a 20-year-old Faroese female with early-onset progressive gait problems, weakness, dysphagia, slurred speech, orthostatic dizziness, and urge incontinence. Neurological examination revealed mild cognitive deficits, dysarthria, broken slow pursuit, hypometric saccades, weakness with spasticity, hyperreflexia, absent ankle reflexes, ataxia, and wide-based, spastic gait. Magnetic resonance imaging displayed atrophy of the cerebellum, brainstem, and spinal cord. Severely prolonged central motor conduction time and lower motor neuron involvement was demonstrated electrophysiologically. Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed hypometabolism of the cerebellum and right frontal lobe. Muscle biopsy revealed chronic neurogenic changes and near-absent immunostaining for Nesprin-1. Next-generation sequencing revealed a previously undescribed homozygous truncating, likely pathogenic variant in the SYNE1 gene. The patient's mother and paternal grandfather were heterozygous carriers of the variant. Her father's genotype was unobtainable. We expand the list of likely pathogenic variants in SYNE1 ataxia with a novel homozygous truncating variant with proximity to the C-terminus and relate it to a phenotype comprising early-onset cerebellar deficits, upper and lower motor neuron involvement and cognitive deficits. Also, we report novel findings of focally reduced frontal lobe FDG-PET uptake and motor evoked potential abnormalities suggestive of central demyelination.

Tetraparetic critically ill patients show electrophysiological signs of myopathy.

INTRODUCTION: Critically ill patients often develop tetraparesis. It has been debated whether this is caused by neuropathy, myopathy, or both. The aim was to determine the incidence of myopathy and neuropathy in weak patients in the intensive care unit by performing several electrophysiological examinations, including quantitative electromyography (qEMG). METHODS: Forty-nine patients referred for electrophysiological examination because of suspected critical illness-related weakness underwent qEMG, nerve conduction studies, and direct muscle stimulation. RESULTS: The qEMG showed signs of myopathy in 33 of 35 patients. Direct muscle stimulation was consistent with myopathy in 31 of 34 patients. Amplitudes of compound muscle action potentials were decreased in all patients. Four patients also had signs of sensory neuropathy, which could not be explained by preexisting medical conditions. CONCLUSIONS: When combined, the results are compatible with muscle dysfunction in all patients. This will help to direct future studies of the pathophysiology of this serious condition. Muscle Nerve 56: 433-440, 2017.

Neurophysiological approach to disorders of peripheral nerve.

Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed.

Lyme neuroborreliosis.

Lyme neuroborreliosis (LNB) designates the nervous system disorders caused by the tick-borne spirochete Borrelia burgdorferi (Bb). The clinical syndromes are usually distinct and are classified as early and the rare late or chronic LNB. Early LNB occurs 3-6 weeks after infection most frequently as a lymphocytic meningoradiculoneuritis (LMR). Symptoms are mainly due to a painful sensory radiculitis and a multifocal motor radiculo-neuritis. Fifty percent have cranial nerve involvement predominantly uni- or bilateral facial nerve palsies. Meningitic symptoms occur primarily in children. Nerve biopsies, autopsies, animal models, and nerve conduction studies showed that the pathology is a lymphocytic perineuritis leading to multisegmental axonal injury of nerve roots, spinal ganglia, and distal nerve segments. Due to meningeal and root inflammation cerebrospinal fluid (CSF) shows lymphocytic inflammation. The only evidence that Bb causes peripheral neuropathy without CSF inflammation is seen in patients with acrodermatitis chronica atrophicans (ACA), a chronic dermatoborreliosis. In the rare chronic or late LNB the pathology and thus the clinical presentation is primarily due to chronic meningitis and meningovascular CNS involvement, whereas the peripheral nervous system is not primarily affected. In early and late LNB the diagnosis is based on a characteristic clinical appearance and CSF inflammation with Bb-specific intrathecal antibody production. Both conditions, but not the ACA-associated neuropathy, respond to antibiotic therapy.

Myopathic EMG findings and type II muscle fiber atrophy in patients with Lambert-Eaton myasthenic syndrome.

OBJECTIVE: Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based on qualitative EMG examination and the histopathological methods were not always clear. The objective of this study was to investigate if the previous EMG findings could be confirmed with quantitative EMG (QEMG) and to describe muscle histology in LEMS. METHODS: QEMG, nerve conduction studies and muscle biopsy were performed in four consecutive LEMS patients. RESULTS: QEMG showed significantly decreased mean MUP duration and muscle biopsy showed marked type II fiber atrophy. CONCLUSION: EMG and biopsy abnormalities mimicking myopathy may often be found in patients with LEMS. SIGNIFICANCE: LEMS is a debilitating, but treatable disease, which often precedes detection of a malignancy and it is therefore of obvious importance to diagnose these patients with speed and certainty. Hence it is important that neurophysiologists and neurologists are aware that EMG and histological abnormalities mimicking myopathy may be found in LEMS patients so that these findings do not prolong or misdirect the diagnostic process in these patients.

[New knowledge of spasticity and its treatment]. / Ny viden om spasticitet og dens behandling.

Spasticity is a frequently used diagnosis, and anti-spastic medication is used widespread. In this systematic review article we highlight difficulties in diagnosing spasticity correctly and thus limit the value of the diagnosis in ensuring the best possible treatment. We review recent neuroscience research and conclude that it is necessary to develop better tools for clinical diagnosis of spasticity in order to avoid potential malpractice and to limit treatment with anti-spastic drugs for patients with documented increased reflex-mediated muscle tone as their main annoyance.

Distinguishing active from passive components of ankle plantar flexor stiffness in stroke, spinal cord injury and multiple sclerosis.

OBJECTIVE: Spasticity is a common manifestation of lesion of central motor pathways. It is essential for correct anti-spastic treatment that passive and active contributions to increased muscle stiffness are distinguished. Here, we combined biomechanical and electrophysiological evaluation to distinguish the contribution of active reflex mechanisms from passive muscle properties to ankle joint stiffness in 31 healthy, 10 stroke, 30 multiple sclerosis and 16 spinal cord injured participants. The results were compared to routine clinical evaluation of spasticity. METHODS: A computer-controlled robotic device applied stretches to the ankle plantar flexor muscles at different velocities (8-200deg/s; amplitude 6°). The reflex threshold was determined by soleus EMG. Torque and EMG data were normalized to the maximal torque and EMG evoked by supramaximal stimulation of the tibial nerve. Passive resistance (the torque response to stretches) was confirmed to be a good representation of the passive stiffness also at higher velocities when transmission in the tibial nerve was blocked by ischemia. RESULTS: Passive torque tended to be larger in the neurological than in the healthy participants, but it did not reach statistical significance, except in the stroke group (p<0.05). Following normalization to the maximal stimulus-evoked torque, the passive torque was found to be significantly larger in neurological participants identified with spasticity than in non-spastic participants (p<0.01). There was no significant difference in the reflex threshold between the healthy and the neurological participants. The reflex evoked torque and EMG were significantly larger in all neurological groups than in the healthy group (p<0.001). Twenty three participants with evidence of hypertonia in the plantar flexors (Ashworth score⩾1) showed normal reflex torque without normalization. With normalization this was only the case in 11 participants. Increased reflex mediated stiffness was detected in only 64% participants during clinical examination. CONCLUSION: The findings confirm that the clinical diagnosis of spasticity includes changes in both active and passive muscle properties and the two can hardly be distinguished based on routine clinical examination. SIGNIFICANCE: The data suggest that evaluation techniques which are more efficient in distinguishing active and passive contributions to muscle stiffness than routine clinical examination should be considered before anti-spastic treatment is initiated.

Hereditary spastic paraplegia caused by the PLP1 'rumpshaker mutation'.

BACKGROUND: Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. Mutations in PLP1 on the X chromosome cause spastic paraplegia type 2 (SPG2) or the allelic Pelizaeus-Merzbacher Disease (PMD). The PLP1 protein is a major myelin protein involved in stabilisation and maintenance of the myelin sheath. The function of the protein has been studied in the rumpshaker mouse, which is a model of SPG2/PMD. OBJECTIVE: To characterise the phenotype of patients with the 'rumpshaker mutation.' PATIENTS: A family with HSP caused by the 'rumpshaker mutation.' RESULTS: The patients showed nystagmus during infancy and had early onset of HSP. They had normal cognition, and cerebral MRI showed relatively unspecific white matter abnormalities on T2 sequences without clear progression. Urinary urgency was reported among the female carriers. MRS of both patients showed increased myo-inositol in the white matter, while decreased N-acetylaspartate was found exclusively in the oldest patient. All evoked potential examinations were compatible with severe central demyelination, while no signs of peripheral demyelination or axonal degeneration were found. (18)F-FDG-PET scans were normal. CONCLUSION: The phenotypes of the patients reported here are the mildest described to be caused by the rumpshaker mutation and represent the mildest form among the spectrum of PLP1 related disorders. No definite symptoms in the female carriers could be ascribed to the mutation. These data suggest the pathology to be an underlying dysmyelinating disorder in combination with a central axonal degeneration.

Post-activation depression of soleus stretch reflexes in healthy and spastic humans.

Reduced depression of transmitter release from Ia afferents following previous activation (post-activation depression) has been suggested to be involved in the pathophysiology of spasticity. However, the effect of this mechanism on the myotatic reflex and its possible contribution to increased reflex excitability in spastic participants has not been tested. To investigate these effects, we examined post-activation depression in Soleus H-reflex responses and in mechanically evoked Soleus stretch reflex responses. Stretch reflex responses were evoked with consecutive dorsiflexion perturbations delivered at different intervals. The magnitude of the stretch reflex and ankle torque response was assessed as a function of the time between perturbations. Soleus stretch reflexes were evoked with constant velocity (175 degrees /s) and amplitude (6 degrees) plantar flexion perturbations. Soleus H-reflexes were evoked by electrical stimulation of the tibial nerve in the popliteal fossa. The stretch reflex and H-reflex responses of 30 spastic participants (with multiple sclerosis or spinal cord injury) were compared with those of 15 healthy participants. In the healthy participants, the magnitude of the soleus stretch reflex and H-reflex decreased as the interval between the stimulus/perturbation was decreased. Similarly, the stretch-evoked torque decreased. In the spastic participants, the post-activation depression of both reflexes and the stretch-evoked torque was significantly smaller than in healthy participants. These findings demonstrate that post-activation depression is an important factor in the evaluation of stretch reflex excitability and muscle stiffness in spasticity, and they strengthen the hypothesis that reduced post-activation depression plays a role in the pathophysiology of spasticity.

Diagnosis of acute neuropathies.

Acute and subacute polyneuropathies present diagnostic challenges since many require prompt initiation of treatment in order to limit axonal degeneration and since an exact and detailed diagnosis is a prerequisite for making the correct choice of treatment. It is for instance of utmost importance to recognize whether the underlying pathological changes are due to demyelination or to axonal degeneration and electrodiagnostic tests can thus in most cases contribute considerably to the securing of an exact diagnosis. The specific and characteristic electrophysiological findings in the different types of acute and subacute neuropathies are discussed, and the various electrophysiological pitfalls and technical problems, which are met in these patients, are mentioned.

Stretch reflex regulation in healthy subjects and patients with spasticity.

In recent years, part of the muscle resistance in spastic patients has been explained by changes in the elastic properties of muscles. However, the adaptive spinal mechanisms responsible for the exaggeration of stretch reflex activity also contribute to muscle stiffness. The available data suggest that no single spinal mechanism is responsible for the development of spasticity but that failure of different spinal inhibitory mechanisms (reciprocal IA inhibition, presynaptic inhibition, IB inhibition, recurrent inhibition) are involved in different patients depending on the site of lesion and the etiology of the spastic symptoms. A recent finding also shows no sign of exaggerated stretch reflexes in muscles voluntarily activated by the spastic patient in general. This is easily explained by the control of stretch reflex activity in healthy subjects. In healthy subjects, the stretch reflex activity is increased during voluntary muscle contraction in part because of depression of the inhibitory mechanisms that are affected in spasticity. In spastic patients, these inhibitory mechanisms are already depressed at rest and cannot be depressed further in connection with a contraction. In relation to most normal movements, antagonist muscles should remain silent and maximally relaxed. This is ensured by increasing transmission in several spinal inhibitory pathways. In spastic patients, this control is inadequate, and therefore stretch reflexes in antagonist muscles are easily evoked at the beginning of voluntary movements or in the transition from flexor to extensor muscle activity. This problem is contradicted by the fact that antispastic therapy to improve voluntary movements should be directed.