The Legacy of the Seminal Publication by Guillain, Barré, and Strohl: The History Behind the Eponym.

The report, "On a syndrome of radiculoneuritis with hyperalbuminosis of the cerebrospinal fluid without a cellular reaction. Remarks on the clinical characteristics and tracings of the tendon reflexes," published in 1916, included superb longitudinal clinical observations of progressive areflexic paralysis in 2 French soldiers, unique laboratory findings from the still new at that time technique of lumbar puncture, and electrophysiological studies. The classic observation of the albumino-cytologic dissociation in the spinal fluid, even over 100 years later, is still one of the most important laboratory findings used by clinicians to confirm the suspected diagnosis of the Acute Inflammatory Demyelinating Polyneuropathy, typically eponymously referred to as Guillain Barré Syndrome (GBS). The contribution of André Strohl, who reported the electrophysiological abnormalities observed in their patients with novel myographic studies of tendon reflexes, led to eventual widespread use of electrodiagnostic techniques in bedside diagnosis of neuromuscular conditions. Since 1916, the clinicopathological spectrum of GBS has expanded continuously, with better understanding of the etiology, pathology, and electrodiagnostic findings. However, most of the seminal observations and conclusions presented by Guillain, Barré, and Strohl have withstood the test of time. Their landmark publication has become a standard of excellence in the history of clinical neurology. Deservedly, "GBS" is one of the most recognized medical eponyms around the world.

Muscle Cramps Do Not Improve With Correction of Vitamin D Insufficiency.

BACKGROUND: Minimal treatment options exist for idiopathic muscle cramps. OBJECTIVE: We evaluated whether correction of vitamin D insufficiency relieved muscle cramps in postmenopausal women. METHODS: We conducted a post hoc analysis of a randomized, double-blind, placebo-controlled trial at a single academic medical center in the Midwest to evaluate the benefits of treating vitamin D insufficiency. Two hundred thirty postmenopausal women participated. Eligible women were ≤75 years old, 5 years past menopause or oophorectomy, or ≥60 years if they had previously undergone hysterectomy without oophorectomy. Women had vitamin D insufficiency at baseline (25-hydroxyvitamin D 14-27 ng/mL). We excluded subjects with a glomerular filtration rate <45 mL/minute. INTERVENTIONS FOR CLINICAL TRIALS: Participants completed food diaries, laboratory studies, and functional tests including the Timed Up and Go test, Physical Activity Scale for the Elderly, Health Assessment Questionnaire (a measure of disability), and pain scores. Subjects recorded muscle cramp frequency and severity using a standardized form at 6 visits over 1 year. RESULTS: During the trial, over half of participants (n=121, 53%) reported muscle cramps. Despite unequivocal vitamin D repletion, vitamin D had no effect on muscle cramps. Pain levels, disability, and dietary potassium predicted presence of cramps. Serum albumin and physical activity were inversely associated with, and disability was positively associated with, severity of muscle cramps. CONCLUSIONS: Further studies are needed to evaluate the link between pain, disability, dietary potassium intake, and muscle cramps.

Ganglion Cysts as a Cause of Ulnar Neuropathy at the Wrist.

INTRODUCTION: The diagnosis of ulnar neuropathy at the wrist traditionally has depended primarily on clinical and electrodiagnostic findings. Magnetic resonance imaging (MRI) and ultrasound have emerged as very important diagnostic tools in diagnosis of focal neuropathies. CASE PRESENTATION: We present clinical, electrodiagnostic, and MRI findings in 2 patients with ulnar neuropathies at the wrist caused by ganglion cysts. DISCUSSION: Ulnar neuropathies at the wrist are common, may present with different patterns of motor and sensory deficits, and can be misdiagnosed. Nerve conduction studies and needle electromyography are essential to assist with anatomical localization of possible lesions. The structural lesions may be well characterized by MRI. CONCLUSIONS: We conclude that MRI is a very useful and important diagnostic tool that may help with diagnosis and therapeutic decisions in patients with ulnar nerve lesions at the wrist. It complements the neurological exam and electrodiagnostic studies. High resolution ultrasound may be an adequate alternative to the MRI.

Antecedents, development, adoption, and application of Duchenne's trocar for histopathologic studies of neuromuscular disorders in the nineteenth century.

Duchenne de Boulogne was one of the founders of clinical neurology. His name has been eponymically linked to the most common form of muscular dystrophy, originally described by him as pseudo-hypertrophic muscular paralysis or myo-sclerotic paralysis. Obtaining muscle biopsy specimens was essential to gain insight about the etiopathogenensis of the disease. Duchenne invented a novel instrument: l'emporte-pièce histologique, also known as "Duchenne's trocar," to perform muscle biopsies. Following Duchenne's design and instructions, a Parisian company, Charrière, constructed the first instrument probably in 1864. That instrument was essential for Duchenne's description of the histopathological abnormalities typical of pseudo-hypertrophic muscular paralysis. The innovative needle-biopsy technique enabled physicians to analyze the spectrum of pathological changes at varying stages of different neuromuscular diseases. Duchenne's trocar was a forerunner of several types of modern muscle-biopsy needles. His invention was instrumental in the development of the disciplines of muscle pathology and clinical myology.

Stormorken Syndrome: A Rare Cause of Myopathy With Tubular Aggregates and Dystrophic Features.

Stormorken syndrome is a rare genetic disorder (MIM 185070) first reported in 1983 with thrombocytopenia, muscle weakness, asplenia, and miosis caused by a mutation of the stromal interaction molecule 1 ( STIM1) gene.1 The muscle weakness is caused by a myopathy with tubular aggregate formation. We report a family in which both child and mother presented with proximal muscle weakness and thrombocytopenia. Histologic, histochemical, and electron microscopy studies were performed on the muscle specimen. It documented accumulation of tubular aggregates and chronic myopathic changes with dystrophic features. Genetic testing revealed that both mother and son carried a missense mutation of c.326A>G in exon 3 of the STIM1 gene, which is novel for Stormorken syndrome. We suggest that patients with unexplained chronic idiopathic thrombocytopenia and proximal weakness have genetic testing for Stormorken syndrome.

Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation.

The background to this study began with the reporting of two Japanese kindreds with the S305N tau mutation. Although the pathological findings in the autopsied cases were well characterized, only limited ante-mortem data were presented. In this study, longitudinal characterization was carried out in two siblings of European ancestry found to have frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) through comprehensive neurobehavioural examinations and other scales at approximate 6-month intervals. Scales included the Mini-Mental State Examination, Short Test of Mental Status, modified motor subtest of the Unified Parkinson's Disease Rating Scale, detailed neuropsychological testing, and the Neuropsychiatric Inventory. Changes in whole-brain volume and ventricular volume were measured from serial MRI studies. All members of the kindred underwent molecular genetic analyses to elucidate the mechanism of inheritance. The missense mutation in tau, S305N, was detected in the proband (onset age 30), who has undergone serial evaluations for almost 4 years. Her older sister (onset age 36) was subsequently found to have the same mutation, and has undergone serial evaluations for 2 years. This mutation is absent in both parents and the only other sibling, and non-paternity was excluded by additional analyses. The siblings have exhibited cognitive and behavioural features typical of FTDP-17, which have proved challenging to manage despite aggressive pharmacological and behavioural therapies. The proband's sister has demonstrated an atypical profile of impairment on neuropsychological testing. Both siblings have developed striking atrophy of the anterior part of temporal lobes and moderate atrophy of the dorsolateral and orbitofrontal cortical regions, which in both cases is relatively symmetrical. The annualized changes in whole-brain volume and ventricular volume, respectively, were -35.2 ml/year (3.23% decrease per year) and +20.75 ml/year (16.93% increase per year) for the proband, and -30.75 ml/year (2.77% decrease per year) and +5.01 ml/year (3.11% increase per year) for the proband's sister. In conclusion, the mutation in these siblings may have arisen during oogenesis in the mother and probably represents germline mosaicism. Although both patients have exhibited the typical cognitive and behavioural features of FTDP-17, one patient is exhibiting an atypical neuropsychological profile. Also, despite a similar topographic pattern of progressive atrophy on MRI, the rates of change in whole-brain volume and ventricular volume between the two patients are quite different. These findings have implications for future drug trial development in FTDP-17 and the sporadic tauopathies.

The Early Use of Blinding in Therapeutic Clinical Research of Neurological Disorders.

We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses.

Two families with MYH7 distal myopathy associated with cardiomyopathy and core formations.

INTRODUCTION: Laing distal myopathy is caused by MYH7 gene mutations. Multiple families have been reported with varying patterns of skeletal and cardiac involvement as well as histopathological findings. CASE SERIES: We report 2 families with p.Glu1508del mutation with detailed electrophysiological and muscle pathology findings. RESULTS: All patients displayed the classic phenotype with weakness starting in the anterior compartment of the legs with a "hanging great toe." It was followed by finger extensors involvement, relatively sparing the extensor indicis proprius, giving the appearance of a "pointing index" finger. All the affected individuals had a dilated cardiomyopathy and core formations on muscle biopsy. Unexpectedly, neurogenic changes were also observed in some individuals. Both families were initially misdiagnosed with either central core disease or hereditary neuropathy. CONCLUSIONS: Recognizing the classic phenotype, screening for cardiac involvement that may be clinically silent, and determining the mode of inheritance help with selecting the appropriate genetic test.

Upper Extremity Multifocal Neuropathy in a 10-Year-Old Boy Associated With NS6S Disaccharide Antibodies.

We present a 10-year-old boy with a predominantly motor multifocal neuropathy with demyelinating and axonal changes with sensory involvement, affecting only one upper extremity. Laboratory studies revealed an elevated titer of immunoglobulin M (IgM) antibodies against the NS6S antigen. He responded to treatment with high dose intravenous immunoglobulins. Focal or multifocal immune-mediated neuropathies are not common in children and may be underdiagnosed.

Friedreich's ataxia associated with mitochondrial myopathy: clinicopathologic report.

A 13-year-old boy with clinical and electrophysiologic findings of Friedreich's ataxia developed unusually prominent myopathy. Skeletal muscle biopsy showed mitochondrial proliferation and structural abnormalities. No mutation was found in skeletal muscle mitochondrial DNA to explain this finding. Molecular genetic and pathologic studies confirmed a diagnosis of Friedreich's ataxia in the proband and affected relatives. Although the Friedreich's ataxia phenotype results from decreased expression of a mitochondrially targeted protein, frataxin, mitochondrial myopathy has not been described as a feature of the disease. The association between the frataxin gene mutation and mitochondrial myopathy in this case suggests that severe or cumulative insults to mitochondrial function may produce myopathic changes in some cases of Friedreich's ataxia. The patient also responded clinically to carnitine supplementation, suggesting a potential palliative therapy for the disease.

Myeloneuropathy from nitrous oxide abuse: unusually high methylmalonic acid and homocysteine levels.

A 23-year-old patient developed diffuse paresthesias and sensory loss. He had mildly reduced serum vitamin B12 (B12) concentration with unusually high levels of methylmalonic acid (MMA) and homocysteine and no evidence of B12 malabsorption. Following parenteral B12 administration, his neurological deficit promptly resolved and B12 and MMA levels normalized, but elevated levels of homocysteine persisted. One year later, he admitted to inhaling nitrous oxide (N2O). After halting N2O abuse his homocysteine level normalized. This case demonstrates the importance of serum homocysteine level measurements in cases of suspected N2O toxicity [corrected].

Motor neuron disease with selective degeneration of anterior horn cells associated with non-Hodgkin lymphoma.

INTRODUCTION: We describe an autopsy-confirmed case of motor neuron disease with selective degeneration of the anterior horn cells associated with a non-Hodgkin lymphoma. METHODS: Case report, including extensive autopsy studies. RESULTS: The patient developed severe fasciculations and then progressive atrophy and weakness several months after the diagnosis and initial treatment of non-Hodgkin lymphoma. As the disease progressed, needle electromyography showed diffuse severe denervation changes including thoracic paraspinal muscles. Autopsy showed severe loss of anterior horn cells with associated gliosis and preservation of cortical spinal tracts and Betz cells. CONCLUSIONS: This case provides an autopsy evidence of severe anterior horn cell degeneration in the course of non-Hodgkin lymphoma, raising the possibility that the neurologic syndrome, characterized by lower motor neuron disease, may represent a paraneoplastic process. Similar cases have been reported previously.

Plasma exchange after initial intravenous immunoglobulin treatment in Guillain-Barré syndrome: critical reassessment of effectiveness and cost-efficiency.

OBJECTIVES: To assess whether intravenous immunoglobulin (IVIG) followed by plasma exchange (PE) is more effective for patients with Guillain-Barré syndrome compared with IVIG alone. METHODS: Retrospective chart review of 46 patients treated for Guillain-Barré syndrome between 1995 and 2005 was performed. Patients were divided into four subgroups based on treatment received (IVIG, PE, IVIG + PE, or neither). Disability grade on admission, after completion of IVIG, and on the day of discharge from hospital (DGD) were assessed. DGD was the primary outcome measure. Duration of hospitalization, costs, duration of symptoms before treatment, and interval between IVIG and initiation of PE were analyzed. RESULTS: Mean disability grade on admission was similar for all groups. DGD was significantly lower for the IVIG group (P < 0.001) than other groups. Compared with admission, patients treated with IVIG + PE had more severe impairment after completion of IVIG (P = 0.044) but did not show significant improvement after PE. Disability grade on admission and DGD scores for patients treated earlier (less than 14 days after onset of symptoms) versus later (greater than 14 days) were not significantly different. Duration of hospitalization was longer in patients receiving IVIG + PE versus IVIG alone (P < 0.001). The cost of treatment was significantly higher in the IVIG + PE subgroup (P < 0.001). No correlation between interval from IVIG to PE onset and DGD score was found. CONCLUSIONS: We found no association between PE after IVIG and improved short-term outcomes of patients with Guillain-Barré syndrome, but there was an association with an increase in cost and duration of hospitalization. There was no association between the timing of PE after IVIG and the short-term outcome. Prospective studies are needed to clarify whether the cost/benefit ratio favors the routine use of this therapeutic approach.

Myopathic dropped head syndrome: an expanding clinicopathological spectrum.

OBJECTIVE: A number of neuromuscular conditions may lead to a dropped head syndrome (DHS), with some patients developing a late onset noninflammatory myopathy affecting only, or predominantly, neck extensor muscles (NEM). The cause, pathogenesis, and nosological classification of this condition are unclear. To further investigate this condition, the authors evaluated the clinical, electrodiagnostic and pathologic findings in seven patients with a myopathic DHS. DESIGN: Analysis of clinical data, electrodiagnostic studies, and muscle biopsies of seven patients, including one set of identical twins, who developed a very late onset myopathy with severe NEM weakness. RESULTS: Age of onset was 61-79 yrs, with the pair of identical twins developing NEM weakness within 1 yr of each other (ages 63 and 64, respectively). Seven patients developed weakness (six slight weakness and one more severe) in muscles other than NEM. The group was characterized by the electromyography (EMG) showing a "myopathic" pattern in cervical paraspinal muscles (7/7), muscle biopsies with nonspecific myopathic changes on histologic stains (7/7), marked abnormalities in NADH dehydrogenase-reacted sections (6/7), desmin-positive sarcoplasmic deposits (1/7), low carnitine levels by biochemical assays (2/7), and mitochondrial changes (3/7). CONCLUSIONS: Myopathic DHS encompasses a wide spectrum of conditions that strongly affect NEM; however, as documented in the monozygotic twins, some patients may suffer from a distinct, genetically determined form of late-onset restricted myopathy leading clinically to DHS.

The astroglial cell that guides nerve fibers from growth cone to synapse in organotypic cultures of the fetal mouse spinal cord.

We present electron microscopic and autoradiographic studies done using organotypic cultures of spinal cord explants excised from 15 days of gestation mouse embryos. Nerve fibers growing from the spinal cord explant carry at their tips immature mitotic astrocytic cells that lead their growth cones. These glial cells divide only during the active phase of neuronal growth, and correspond ultrastructurally to radial glia. They provide a specific cellular substrate for neuronal growth. Some growth cones form axoglial synapses with smooth membranes of immature glial cells. In contrast, maturing glial cells sprout cytoplasmic processes that tightly wrap individual growth cones and effectively arrest their growth. Next, the processes gather nerve endings into islets and nerve fibers into bundles. After internalizing nerve endings, the glial processes withdraw, bringing the endings into contact with each other. The direct neuronal appositions lead to the transformation of growth cones into presynaptic endings, signaled by their collection of presynaptic vesicles. Clustering of the vesicles at presynaptic axoglial or axodendritic membranes indicates the onset of synaptogenesis-completed by differentiation of spinous and compound synapses. Concomitant with the progress of synaptogenesis, astrocytic investment within the neuropil progressively diminishes. The differentiating astrocytic processes show secretory and tethering activity toward nerve fibers and their endings. Our observations demonstrate that astroglial cells-depending on their developmental stage-first promote and then arrest neuronal growth, and induce synaptogenesis. Thus, at any time, the growing nerve fibers are not only supported but also controlled by the astroglial cells.

Subclinical sensory involvement in monomelic amyotrophy.

An 18-year-old woman presented with weakness and atrophy in her hand without associated sensory symptoms, preceding events, or structural abnormalities on neuroimaging. No sensory deficits were detected on neurologic examination. Electrophysiological studies showed not only the expected motor findings for monomelic amyotrophy (MA) in the affected limb, but also markedly reduced sensory nerve action potentials when compared with the unaffected side. These findings suggest that subclinical sensory involvement can exist in patients with otherwise classic presentations of MA.

Clinical utility of videofluorography with concomitant Tensilon administration in the diagnosis of bulbar myasthenia gravis.

Myasthenia gravis (MG) classically presents with ocular, bulbar, and predominantly proximal muscle weakness. Isolated bulbar symptoms occur in less than 25% of cases and can mimic stroke (1-3). If left untreated, MG can lead to significant morbidity and mortality, including myasthenic crisis and recurrent aspiration pneumonia. We describe a case of a 68-year-old man who presented with isolated bulbar symptoms. We used a novel approach to diagnosis which included a videofluorographic swallow study with concomitant Tensilon (edrophonium) injection.

Effective treatment of severe finger flexion weakness in inclusion body myositis using tendon transfers.

A 70-year-old-patient with severe, disabling weakness of finger flexion caused by inclusion body myositis (IBM) underwent surgical treatment with tendon transfers in his dominant (right) upper extremity. His finger flexion markedly improved and he regained the ability to write, use tools, and engage in activities that require good hand function. Treatment of disabling finger weakness with tendon transfers can be very effective in some IBM patients.

Unilateral calf hypertrophy seen in lumbosacral stenosis: case report and review of the literature.

STUDY DESIGN: A case report of a patient with neurogenic unilateral calf hypertrophy and review of the literature are reported. OBJECTIVES: To provide further evidence that S1 radiculopathy is predisposed to develop neurogenic muscle hypertrophy. SUMMARY OF BACKGROUND DATA: Calf hypertrophy, specifically hypertrophy of the gastrocnemius muscle, is a rare but recognized presentation of S1 and less commonly L5 radiculopathies. The pathophysiology of this is incompletely understood. METHODS: We present a 59-year-old patient with painless progressive distal right leg weakness and calf enlargement. Electrodiagnostic studies and MAGNETIC RESONANCE IMAGING scanning were performed to evaluate the extent and cause of radicular damage as the etiology for unilateral calf hypertrophy. RESULTS: Examination and electrodiagnostic studies revealed right L5, right S1, and left L5 radiculopathies. Imaging studies demonstrated lumbar stenosis at L3-L4, L4-L5, and L5-S1 vertebral levels as well as L4-L5 and L5-S1 foraminal stenosis. After decompressive surgery the progressive nature of the patient's symptomatology halted, and he had partial resolution of his deficits. CONCLUSION: Although the patient had bilateral L5 radiculopathies, he only had hypertrophy in the distribution of his right S1 radiculopathy. This supports the hypothesis that dysfunction of the S1 nerve root or its distribution is a predisposing factor to develop neurogenic muscle hypertrophy. Furthermore, patients presenting with unilateral calf hypertrophy need a careful diagnostic evaluation for S1 radiculopathy as well as to exclude asymmetric presentation of systemic neuromuscular conditions.