Congenital myasthenic syndrome: Ten years clinical experience from a quaternary care south-Indian hospital.

BACKGROUND: To ascertain the frequency, clinical spectrum and outcome of congenital myasthenic syndrome (CMS) patients who reported to the neuromuscular division of our quaternary medical center during the past ten years. METHODS: We performed a retrospective analysis of all the CMS patients who reported to us during the study period. RESULTS: Twenty-one patients of CMS attended our quaternary hospital over the past ten years. The median follow-up was 24 (IQR: 16.5-67.3) months. All the patients showed an overall improvement in the last follow up. The diagnosis of CMS could be genetically confirmed in seven cases. Four patients had COLQ mutation, two had CHRNε mutation and one had MUSK mutation. All the cases of COLQ mutation and one case of MUSK mutation had a limb-girdle (LG) presentation. Our study and review of literature imply that CMS should be suspected in cases of seronegative myasthenia gravis cases if the onset is at less than 20 years and strongly so if the onset is within the first two years of life. In addition, a positive family history, delayed motor milestones, and a poor response to immune-modulators should be actively sought for as indicators of CMS.

In vivo dosimetry with optically stimulated luminescent dosimeters for conformal and intensity-modulated radiation therapy: A 2-year multicenter cohort study.

PURPOSE: Optically stimulated luminescent dosimeters (OSLDs) are utilized for in vivo dosimetry (IVD) of modern radiation therapy techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Dosimetric precision achieved with conventional techniques may not be attainable. In this work, we measured accuracy and precision for a large sample of clinical OSLD-based IVD measurements. METHODS AND MATERIALS: Weekly IVD measurements were collected from 4 linear accelerators for 2 years and were expressed as percent differences from planned doses. After outlier analysis, 10,224 measurements were grouped in the following way: overall, modality (photons, electrons), treatment technique (3-dimensional [3D] conformal, field-in-field intensity modulation, inverse-planned IMRT, and VMAT), placement location (gantry angle, cardinality, and central axis positioning), and anatomical site (prostate, breast, head and neck, pelvis, lung, rectum and anus, brain, abdomen, esophagus, and bladder). Distributions were modeled via a Gaussian function. Fitting was performed with least squares, and goodness-of-fit was assessed with the coefficient of determination. Model means (µ) and standard deviations (σ) were calculated. Sample means and variances were compared for statistical significance by analysis of variance and the Levene tests (α = 0.05). RESULTS: Overall, µ ± σ was 0.3 ± 10.3%. Precision for electron measurements (6.9%) was significantly better than for photons (10.5%). Precision varied significantly among treatment techniques (P < .0001) with field-in-field lowest (σ = 7.2%) and IMRT and VMAT highest (σ = 11.9% and 13.4%, respectively). Treatment site models with goodness-of-fit greater than 0.90 (6 of 10) yielded accuracy within ±3%, except for head and neck (µ = -3.7%). Precision varied with treatment site (range, 7.3%-13.0%), with breast and head and neck yielding the best and worst precision, respectively. Placement on the central axis of cardinal gantry angles yielded more precise results (σ = 8.5%) compared with other locations (range, 10.5%-11.4%). CONCLUSIONS: Accuracy of ±3% was achievable. Precision ranged from 6.9% to 13.4% depending on modality, technique, and treatment site. Simple, standardized locations may improve IVD precision. These findings may aid development of patient-specific tolerances for OSLD-based IVD.

Multipoint incremental motor unit number estimation versus amyotrophic lateral sclerosis functional rating scale and the medical research council sum score as an outcome measure in amyotrophic lateral sclerosis.

INTRODUCTION: Monitoring the disease progression in amyotrophic lateral sclerosis (ALS) is a challenge due to different rates of progression between patients. Besides clinical methods to monitor disease progression, such as the ALS functional rating scale (ALSFRS) and the medical research council (MRC) sum score, quantitative methods like motor unit number estimation (MUNE) are of interest. OBJECTIVE: The objective of the present study is to evaluate the rate of progression in ALS using multipoint incremental MUNE and to compare MUNE, ALSFRS and MRC sum score at baseline and at 6 months for progression of the disease. MATERIALS AND METHODS: Multipoint incremental MUNE using median nerve, ALS-FRS and MRC sum score was carried out in 29 ALS patients at baseline and then at 6 months. RESULTS: Of the 29 ALS patients studied, the mean MUNE at baseline was 21.80 (standard deviation [SD]: 19.46, range 4-73), 15.9 in the spinal onset group (SD: 14.60) and 30.16 (SD: 22.89) in the bulbar onset group. Spinal onset patients had 74.02% of baseline MUNE value while bulbar onset patients had only 24.74% baseline value MUNE at 6 months follow-up (Unpaired t-test, P = 0.001). ALSFRS and MRC sum score showed statistically significant decline (P < 0.001) at 6 months follow-up. MUNE had the highest sensitivity for progression of the disease when compared to the ALS FRS and MRC sum score. CONCLUSION: Multipoint incremental MUNE is a valuable tool for outcome measure in ALS and other diseases characterized by motor unit loss. The rate of decline of multipoint incremental MUNE is more sensitive than that of MRC sum score and ALSFRS-R, when expressed as the percentage change from baseline.

Hypertrophic pachymeningitis in a patient with Takayasu arteritis: One more association?

Hypertrophic pachymeningitis (HP) is a rare chronic inflammatory disease of the dura mater, described in association with various infections, systemic vasculitides such as Wegener's granulomatosis and giant cell arteritis. However, HP in association with Takayasu arteritis (TA) has not been described. We report a young woman who presented with headache, seizures, and right third and fourth cranial neuropathy. Magnetic resonance imaging of the brain showed HP in bifrontal and right temporal region extending to cavernous sinus. She was also found to have systemic hypertension, stenosis of left subclavian, and left renal artery with narrowing of abdominal aorta, satisfying the diagnostic criteria for TA. A detailed evaluation for secondary causes of HP failed to reveal an alternative etiology. This report describes an unusual association of HP in a patient with TA, also emphasizing that seizures and cranial neuropathy may further expand the spectrum of neurological manifestations in patients with TA.

Vascular parkinsonism: what makes it different?

Vascular parkinsonism (VP) accounts for 2.5-5% of all cases of parkinsonism in various population based and clinical cohort studies. VP develops as a result of ischaemic cerebrovascular disease, so aetiologically it is classified as secondary parkinsonism. It has been variably referred to in the literature as arteriosclerotic parkinsonism, vascular pseudo-parkinsonism, and lower body parkinsonism. The most important consideration while making a diagnosis of VP should be to differentiate VP from Parkinson's disease (PD) because of prognostic and therapeutic implications. The salient clinical features in VP which differentiate it from PD are presentation with postural instability and falls rather than with upper limb rest tremor or bradykinesia; short shuffling parkinsonian gait in VP is accompanied by a wider base of stance and variable stride length (parkinsonian-ataxic gait), absence of festination, frequent occurrence of pyramidal signs, and early subcortical dementia. In a patient where the clinical features are suggestive of VP the clinical diagnosis can be supported by demonstration of diffuse white matter lesions and/or strategic subcortical infarcts in the MRI of the brain. The therapeutic options in VP are limited to levodopa, and a poor or non-sustained response to levodopa is another differentiating feature between VP and PD.

Kinaesthetic ipsilateral and crossed extensor plantar response: A new way to elicit upgoing toe sign (Babinski response)?

We describe a phenomenon of "kinaesthetic extensor plantar response" in advanced pyramidal dysfunction, an interesting observation noted in a patient with dorsal myelopathy. A 44-year-old woman presented with one-year history of gradually progressive weakness and stiffness of both lower limbs along with urge incontinence of urine. Examination showed spontaneous elicitation of extensor plantar response while assessing the tone by rolling method as well as on noxious stimulation of the thigh. Magnetic resonance imaging (MRI) of the dorsal spine and digital subtraction angiography showed the presence of spinal dural arteriovenous fistula causing myelopathy. This case exemplifies the fact that in advanced pyramidal dysfunction, not only the receptive field of Babinski reflex may extend to the leg or thigh, but may also integrate with other modalities of stimulation, such as the rolling movement. The possible underlying pathophysiology of such a phenomenon is discussed.

Factors associated with misdiagnosis of acute stroke in young adults.

Misdiagnosis or delayed diagnosis of acute ischemic stroke can result in neurologic worsening or a missed opportunity for thrombolysis. Because stroke in young adults is less common than stroke in the elderly, we sought to determine clinical characteristics associated with misdiagnosis of stroke in young adults. Patients from the prospectively maintained Young Stroke Registry in our comprehensive stroke center were reviewed. Demographic information, past medical history, presentation within the 3-hour time window, and outcomes were assessed. We compared patients misdiagnosed and those correctly diagnosed to identify factors associated with misdiagnosis of acute stroke. A total of 57 patients aged 16-50 were enrolled in the registry during 2001-2006. Eight patients (14%; 4 men and 4 women; mean age, 38 years) were misdiagnosed. Seven of these 8 patients were discharged from the emergency department initially. Patients age <35 years (P = .05) and patients with posterior circulation stroke (P = .006) were more likely to be misdiagnosed. All 8 misdiagnosed patients were initially evaluated at hospitals that were not certified primary stroke centers. Patients presenting with vertebrobasilar territory ischemia have a greater rate of misdiagnosis. Our study demonstrates the increasing need for "young stroke awareness" among emergency department personnel. Initial misdiagnosis can potentially lead to a lost opportunity for thrombolysis in otherwise good candidates.

Anomalous origin of the middle meningeal artery from the posterior inferior cerebellar artery.

Various anastomosis and aberrant origins of the middle meningeal artery (MMA) have been documented in literature. However, there has been no report of its origin from the posterior inferior cerebellar artery (PICA) or its branches. In this report, we discuss an anomalous origin of the MMA from the PICA. Also, we discuss the embryological and anatomical development of the MMA. Imaging identification of the origin of the MMA is important while planning surgical and endovascular interventions in the region of the skull base.

Acute endovascular recanalization therapy in wake-up stroke.

BACKGROUND AND PURPOSE: Up to 15-25% of patients with ischemic stroke wake up with their deficits. Because of the uncertainty about the time of onset, these patients are generally not offered thrombolytic therapy. Some of these wake-up stroke patients may be eligible for acute endovascular stroke therapy based on hyperacute CT or MR imaging independent of the time window. REPORT: We report two patients with acute ischemic stroke whose symptoms were present upon awakening and who were successfully treated with endovascular interventions. RESULTS: The first patient was discharged with complete neurological recovery on second day after endovascular intervention. The second patient went home on fifth day with a mild left facial paresis and left arm drift. Both these patients did not have any neurological deficit on 18-month follow up. CONCLUSIONS: Some patients who present with stroke on awakening may be candidates for thrombolytic therapy or recanalization techniques irrespective of mode of therapy (intravenous, intravenous+intra-arterial or intra-arterial tPA alone). Further randomized, controlled studies are warranted to safely identify those candidates who would benefit from thrombolysis and endovascular interventions in ischemic wake-up strokes.

Repetitive compound muscle action potentials in electrophysiological diagnosis of congenital myasthenic syndromes: a case report and review of literature.

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of disorders, characterized by dysfunction of neuromuscular junction (NMJ) transmission. These syndromes are genetically inherited and are present since birth. Some have characteristic clinical or electrodiagnostic features but in many cases determination of the specific form requires genetic studies or specialized morphological and electrophysiological studies on muscle tissue. We report a case of a 4-year-old boy with progressive ptosis and limitation of ocular movements who was diagnosed as slow-channel CMS based on the characteristic electrodiagnostic features. Repetitive compound muscle action potentials (R-CMAPs) were recorded after single nerve stimulus, with decremental response after repetitive trains performed at 3 Hz. CMSs are at times clinically difficult to distinguish from acquired myasthenia. The characteristic clinical and electrodiagnostic features help in the diagnosis and enable rational therapy. In this article we discuss the characteristics of synaptic R-CMAPs.

Clinical, electrophysiologic, and histopathologic profile, and outcome in idiopathic inflammatory myositis: An analysis of 68 cases.

OBJECTIVES: To study the electroclinical and histopathologic profile of idiopathic inflammatory myositis (IIM) with reference to prognosis and survival rate. MATERIALS AND METHODS: Diagnosis of IIM was based on the Bohan and Peter criteria. Patients who improved and those whose condition worsened or who expired due to IIM per se at last follow-up were classified to have favorable and poor outcomes, respectively. Fisher's exact test was used for univariate analysis of prognostic factors. RESULTS: The study cohort consisted of consecutive 68 patients with IIM. The mean age at diagnosis was 36.5 years and females constituted 71%. Of these patients, 62% had definite IIM, 49% had polymyositis, 20% had dermatomyositis, and 29% had overlap syndrome. The mean follow-up period was 5.4 years. Prednisolone alone was used in 55 (80%), and azathioprine (1-3 mg/kg/day) alone in 12 (17.6%) as the initial treatment. Relapse of IIM with drug withdrawal was seen in 15 patients (22%); 70% had favorable outcome and 16% had expired. The treatment delay of ≤6 months (P = 0.001), absence of cardiac or lung involvement (P < 0.001), and positive biopsy (P = 0.033) were predictive of a favorable prognosis in the univariate analysis. In multivariate analysis, only the duration of illness of ≤6 months (P = 0.008) and the absence of cardiac or lung involvement (P = 0.001) predicted the favorable outcome at last follow-up. Cumulative survival rate was 95% at 1 year, 86% at the 5th year, and 80% at the 10th year. CONCLUSIONS: Approximately, two-thirds of the patients showed good electroclinical and histopathologic correlations and an equal number improved with treatment. The treatment delay (≥6 months), presence of cardiac or pulmonary involvements, and negative muscle biopsy are bad prognostic factors.

Factor v leiden mutation in reocclusion after intra-arterial thrombolysis.

BACKGROUND AND PURPOSE: Reocclusion of intracranial arteries after successful recanalization is associated with poor clinical outcome. The role of Factor V Leiden mutation in intracranial arterial thrombosis/rethrombosis is unclear. SUMMARY OF REPORT: We report the case of a patient who developed recurrent reocclusions of the middle cerebral artery after intra-arterial thrombolysis for acute ischemic stroke. The patient subsequently underwent transcatheter clot retrieval followed by successful stent-supported angioplasty of the occluded segment. He underwent a detailed workup for thrombophilia. The patient was detected to be heterozygous for Factor V Leiden mutation without any other cause for thrombophilia. CONCLUSIONS: Factor V Leiden mutation could be a contributing etiology for reocclusion after endovascular interventions in stroke. Systematic studies looking for thrombophilic mutations in patients with arterial reocclusion might be warranted.

Electrodiagnostic and clinical aspects of Guillain-Barré syndrome: an analysis of 142 cases.

BACKGROUND: The incidence of Guillain-Barré syndrome (GBS) and its subtypes varies throughout the world. OBJECTIVE AND METHODS: We present a retrospective analysis of 142 GBS cases, treated at our center, aimed at classifying GBS electrophysiologically, to study the sequential electrophysiological changes in cases with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and to look for any clinical and cerebrospinal fluid parameters that can also help in distinguishing the subtypes. RESULTS: One hundred twenty-one (85.2%) cases had AIDP, 15 (10.6%) had acute motor axonal neuropathy, and 6 (4.2%) were unclassifiable. CONCLUSIONS: Motor conduction blocks and temporal dispersion could be observed from days 3 and 5 onward, respectively. Progression of motor conduction slowing in AIDP was most impressive in the median nerves. Varying affection of deep tendon reflexes, cranial nerves, and cerebrospinal fluid albuminocytological dissociation can also help make a distinction between AIDP and acute motor axonal neuropathy. Sural sparing, a marker of demyelinating neuropathy, is more commonly seen in later than in early stages of AIDP.

Muscle channelopathies and electrophysiological approach.

Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutation in genes coding for skeletal muscle voltage ionic channels. Familial periodic paralysis and nondystrophic myotonias are disorders of skeletal muscle excitability caused by mutations in genes coding for voltage-gated ion channels. These diseases are characterized by episodic failure of motor activity due to muscle weakness (paralysis) or stiffness (myotonia). Clinical studies have identified two forms of periodic paralyses: hypokalemic periodic paralysis (hypoKPP) and hyperkalemic periodic paralysis (hyperKPP), based on changes in serum potassium levels during the attacks, and three distinct forms of myotonias: paramyotonia congenita (PC), potassium-aggravated myotonia (PAM), and myotonia congenita (MC). PC and PAM have been linked to missense mutations in the SCN4A gene, which encodes alpha subunit of the voltage-gated sodium channel, whereas MC is caused by mutations in the chloride channel gene (CLCN1). Exercise is known to trigger, aggravate, or relieve symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. Five electromyographic (EMG) patterns (I-V) that may be used in clinical practice as guides for molecular diagnosis are discussed.

Guillain-Barre syndrome in children and adolescents--a retrospective analysis.

In this study, 55 cases of Guillain-Barre syndrome (GBS) in children and adolescents of 2-18 years of age were analysed retrospectively to study the clinical profile and to evaluate the prognostic value of reduced compound muscle action potential (CMAP) on the need for ventilation and functional outcome. Of the 28 boys and 27 girls 87.3% were bed-bound at peak deficit. Other features were as follows: Bifacial weakness-75%, bulbar weakness-56.4%, need for assisted ventilation-41.8% and albuminocytological dissociation-65.9%. In the ventilated and non-ventilated group no difference was noted in the incidence of reduced CMAP amplitude (p-value > 0.5). At 3 months 83.3% and at 6 months 80.8% cases were ambulant with support. Reduced CMAP amplitude of less than 20% of the lower limit of the normal in at least 2 nerves did not predict the need for ventilation or the chance of independent walking at 3 or 6 months.

Intraoperative electrocorticography in epilepsy surgery: useful or not?

Intraoperative electrocorticography (ECoG) has been traditionally used in the surgical management of medically refractory partial epilepsies to identify the location and limits of the epileptogenic area, to guide the extent of resection, and to assess its completeness. Although in clinical use for many years, the basic questions regarding indications and limitations of this method has remained unanswered. ECoG plays a major role in tailored temporal lobectomies, whereas, it serves no practical purpose in standard resection of medial temporal lobe epilepsy (TLE) with magnetic resonance imaging (MRI) evidence of mesial temporal sclerosis (MTS). Residual hippocampal spikes, unaltered by resection, correlate with a greater proportion of seizure recurrence. Intraoperative hippocampal ECoG can allow sparing of functionally important hippocampus, thus minimising postoperative memory decline. ECoG eminently aids removal of developmental malformations of brain, and most importantly, the excision of highly epileptogenic cortical dysplasias (CDs) for deciding the extent of resection for best seizure control. The ECoG can be a valuable tool during multiple subpial transections (MST).

Anomalous superficial radial nerve: a patient with probable autosomal dominant inheritance of the anomaly.

The sensory symptoms due to lesions of the superficial branch of the radial nerve are usually limited to the dorsolateral area of the hand. We describe a 40-year-old woman who presented with numbness of the dorsomedial aspect of the right hand following arthroplasty of the wrist. Clinically, the sensory loss suggested a lesion of the dorsal branch of the ulnar nerve. However, nerve conduction studies showed that the sensory loss was due to a lesion of a branch of the superficial branch of the radial nerve. The patient had bilateral, anomalous innervation of the dorsum of the hand-the dorsal branch of the ulnar nerve could not be demonstrated with nerve conduction techniques and the superficial branch of the radial nerve innervated most of the dorsum of the hand. Antidromic stimulation of the dorsal branch of the ulnar nerve and superficial branch of the radial nerve with paired surface recording of sensory nerve action potentials from the dorsolateral (radial side) and dorsomedial (ulnar side) hand is useful for evaluating this anomaly. Our patient had two children, one of them with a similar anomaly. This suggests an autosomal dominant inheritance of the anomaly.