A case of glial fibrillary acidotic protein (GFAP) meningoencephalitis with rheumatoid arthritis.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an inflammatory disease of the central nervous system (CNS), which affects various regions in the CNS, presenting by variable clinical manifestations. Meningoencephalitis is the most common clinical presentation and association with autoimmune disorders has been reported in about 20% of these patients. Diagnosis is confirmed by the presence of CSF or serum immunoglobulin-G (IgG) against GFAP. The reported case is a 53-year-old woman with the history of long-standing rheumatoid arthritis who first presented with acute-onset dizziness and gait disturbance, periventricular linear and radial enhancement pattern on MRI, and normal CSF analysis, successfully treated with an increase in the dose of oral steroids. After a year she had a subacute-onset, moderate to severe holocephalic headache, normal neurologic examination and CSF analysis, and bilateral diffuse, pachymeningeal, and leptomeningeal enhancement on MRI. According to her Brain MRI imaging with relapsing remitting course steroid responsive ataxia and aseptic meningitis, her serum was tested for GFAP IgG antibodies which was positive. The reported patient is the first in the literature reported pachymeningitis in GFAP astrocytopathy. This case highlights the co-occurrence of rheumatoid arthritis with GFAP-associated astrocytopathy, and expands on the previously reported cases with similar association. This might also suggest a common immune pathogenesis.

Fulminant encephalitis as a sole manifestation of COVID-19.

Novel coronavirus (SARS-CoV-2) occurred in December 2019 in Wuhan, China, and has become a global health emergency. Coronavirus primarily is a respiratory virus, but it has been detected in the brain and cerebrospinal fluid of infected individuals. The present report describes a case of fulminant encephalitis in a patient affected by COVID-19.

Non-invasive Transcranial Electrical Stimulation in Movement Disorders.

Dysfunction within large-scale brain networks as the basis for movement disorders is an accepted hypothesis. The treatment options for restoring network function are limited. Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation are now being studied to modify the network. Transcranial electrical stimulation (tES) is also a portable, cost-effective, and non-invasive way of network modulation. Transcranial direct current stimulation and transcranial alternating current stimulation have been studied in Parkinson's disease, dystonia, tremor, and ataxia. Transcranial pulsed current stimulation and transcranial random noise stimulation are not yet studied enough. The literature in the use of these techniques is intriguing, yet many unanswered questions remain. In this review, we highlight the studies using these four potential tES techniques and their electrophysiological basis and consider the therapeutic implication in the field of movement disorders. The objectives are to consolidate the current literature, demonstrate that these methods are feasible, and encourage the application of such techniques in the near future.

Assessing the effect of current steering on the total electrical energy delivered and ambulation in Parkinson's disease.

Vertical current steering (vCS) divides current between multiple contacts, which reduces radial spread to fine-tune the electric field shape and improves neuroanatomical targeting. vCS may improve the variable responsiveness of Parkinsonian gait to conventional deep brain stimulation. We hypothesized that vCS elicits greater improvement in ambulation in Parkinson's disease patients compared to conventional, single-contact stimulation. vCS was implemented with divisions of 70%/30% and 50%/50% and compared to single-contact stimulation with four therapeutic window amplitudes in current-controlled systems. Walking at a self-selected pace was evaluated in seven levodopa-responsive patients. Integrative measures of gait and stimulation parameters were assessed with the functional ambulation performance (FAP) score and total electrical energy delivered (TEED), respectively. A two-tailed Wilcoxon matched-pairs signed rank test assessed the effect of each stimulation condition on FAP and TEED and compared regression slopes; further, a two-tailed Spearman test identified correlations. vCS significantly lowered the TEED (P < 0.0001); however, FAP scores were not different between conditions (P = 0.786). Compared to single-contact stimulation, vCS elicited higher FAP scores with lower TEED (P = 0.031). FAP and TEED were positively correlated in vCS (P = 2.000 × 10-5, r = 0.397) and single-contact stimulation (P = 0.034, r = 0.205). Therefore, vCS and single-contact stimulation improved ambulation similarly but vCS reduced the TEED and side-effects at higher amplitudes.

Comparison of proximal and distal corticosteroid injections for carpal tunnel syndrome.

INTRODUCTION: Evidence for the efficacy of distal corticosteroid injection compared with proximal injection in carpal tunnel syndrome (CTS) is inadequate. METHODS: We conducted a randomized, double-blind noninferiority trial of 131 wrists with CTS. Forty milligrams of methylprednisolone was injected medial to the palmaris longus tendon 2 cm proximal to the wrist crease, or at the volar aspect, 2 to 3 cm distal to the wrist crease. Proximal & distal groups received a placebo. The primary outcome was difference in CTS Symptom Severity Scale (SSS) score at 1 month. Secondary outcome measures included the difference in SSS score at 3 months, Functional Status Scale (FSS) score at 1 and 3 months, and pain of injections. RESULTS: No significant differences were noted between groups in scores on the SSS and FSS. Pain was lower in the proximal group compared with the distal group. DISCUSSION: Corticosteroid injections for CTS distal to the wrist are not inferior to proximal injections, yet they are more painful.

Focal limb dystonia and tremor: Clinical update.

The association between tremor and dystonia has been known for many decades. Dystonic tremor is seen in the body part affected with dystonia. Tremor and dystonia can also co-exist in different body parts. Subtle dystonic posturing can be missed in patients with upper limb tremor and these patients are often misdiagnosed as essential tremor. Careful clinical examination and electrophysiology may help in differentiating classical essential tremor from dystonic tremor. Writer's cramp, a common focal hand dystonia can mimic primary writing tremor when the dystonic posturing is subtle. Oral medications have limited therapeutic efficacy. Botulinum toxin is considered as first line therapy for focal limb dystonia and is also effective in the treatment of tremor. Surgical options are reserved for cases refractory to medical therapy. In this review, we summarize the current state of knowledge of focal limb dystonia and tremor with a focus on underlying neurophysiology in these conditions.

Zona incerta deep-brain stimulation in orthostatic tremor: efficacy and mechanism of improvement.

BACKGROUND: Orthostatic tremor is a rare hyperkinetic movement disorder that is characterized by a 13-18 Hz tremor in both legs while standing. Deep-brain stimulation of the caudal zona incerta has re-emerged as an alternate target for tremor control in various etiologies. OBJECT: Explore the clinical efficacy and mechanism of action of caudal zona incerta deep-brain stimulation in orthostatic tremor. METHODS: Four patients (63.1 ± 4.1 years, female = 50%) with orthostatic tremor were recruited for this open label study (63.1 ± 4.1 years, female = 50%). In two patients, the electrodes were externalized to determine the effectiveness of caudal zona incerta as a target. Surface EMG (leg muscles), EEG (leg motor cortex) and caudal zona incerta local field potential recordings were recorded. Data were recorded in sitting and standing positions with stimulation OFF and ON. RESULTS: EMG frequency analysis showed tremor frequency at 13-17 Hz. EMG-EEG coherence was found in the tremor frequency band and double tremor frequency band. EMG-caudal zona incerta coherence was higher in the tremor frequency band, while EEG coherence was higher in the double tremor frequency band. Upon stimulation, there was a selective reduction in tremor frequency band EEG-EMG coherence in all patients. All the patients had reduction in feeling of unsteadiness and increase in the stance duration. CONCLUSIONS: Bilateral caudal zona incerta deep-brain stimulation is effective in refractory orthostatic tremor. Two independent central oscillations were found at tremor and double tremor frequency. Zona incerta DBS produces improvement in OT patients possibly by modifying the abnormal oscillatory proprioceptive input from leg muscles. Frequent changes in deep-brain stimulation settings were required for maintaining the clinical benefit.

Neurological Worsening After Implantable Pulse Generator Replacement.

BACKGROUND: Most of the implantable pulse generators (IPGs) in deep brain stimulation (DBS) used to date are non-rechargeable requiring regular replacements. IPG replacement is a minor surgical procedure, but adverse events including neurological worsening have been reported. In this study, we determine the possibility of neurological worsening after IPG replacement in Parkinson's disease (PD) cases on chronic DBS therapy (CDT) and its electrophysiological basis along with the therapeutic interventions used to alleviate them. METHODS: This study is a retrospective chart review of PD cases on CDT followed at London Movement Disorders Centre from January 2010 to December 2016. Included cases were those who underwent one or more IPG replacement. RESULTS: A total of 45 PD cases on CDT underwent 62 IPG replacements involving 121 channels. Neurological worsening was observed in 16 (35.5%) cases following 17 (27.4%) IPG replacements, all following dual-channel IPG replacements. Tremor (41.2%), speech (35.3%), and gait (23.5%) worsened most commonly. Deviation from the pre-replacement parameters including voltage and impedance resulting in change in total electrical energy delivered (TEED) was the most common electrophysiological correlate, observed in 82.4% (14/17) IPGs having neurological worsening. This included switched laterality in a dual-channel IPG. Neurological worsening in the remaining 17.6% cases was hardware-related. CONCLUSION: Neurological worsening followed 27.4% of IPG replacements in PD cases on CDT with approximately 82.4% of these being avoidable by carefully monitoring stimulation parameters to match pre-replacement TEED values.

Évolution défavorable de l'état neurologique de patients après le remplacement de leur générateur d'impulsions implantable. CONTEXTE: La plupart des générateurs d'impulsions implantables (GII) utilisés jusqu'à présent lors de séances de stimulation cérébrale profonde (SCP) ne peuvent être rechargés, ce qui nécessite des remplacements à intervalles réguliers. Même si le remplacement d'un GII demeure une intervention chirurgicale mineure, des manifestations indésirables, notamment la détérioration neurologique de certains patients, ont été signalées. Dans cette étude, nous voulons donc déterminer, après le remplacement d'un GII, les possibilités de détérioration neurologique de patients atteints de la maladie de Parkinson (MP). Rappelons que ces patients ont entrepris, de concert avec d'autres interventions thérapeutiques, des séances de SCP en vue de réduire leurs douleurs chroniques. MÉTHODES: Nous avons donc passé en revue de façon rétrospective les dossiers de patients atteints de MP et bénéficiant de séances de SCP. Ces patients avaient été suivis au London Movement Disorders Centre de janvier 2010 à décembre 2016. Soulignons aussi qu'ils ont subi un ou plusieurs remplacements de leur GII en cours d'étude. RÉSULTATS: Au total, 45 patients atteints de MP bénéficiant de SCP visant à soulager leurs douleurs chroniques ont été visés par 62 remplacements de GII impliquant 121 canaux. Une détérioration neurologique a été observée chez 16 patients (35,5 %) à la suite de 17 (27,4 %) remplacements de GII, lesquels ayant tous été effectués à la suite de remplacements de GII double canal. Parmi les aspects s'étant le plus souvent détériorés, mentionnons des tremblements (41,2 %), la parole (35,3 %) et la démarche (23,5 %). Une déviation par rapport aux paramètres de pré-remplacement, ce qui inclut la tension et l'impédance, tous deux pouvant entraîner des modifications à l'énergie électrique totale produite, est apparue comme le corrélat électro-physiologique le plus fréquent. Ce dernier a en effet été observé dans 82,4 % (14/17) des remplacements de GII ayant entraîné une détérioration neurologique. Cela a inclus notamment une latéralité inversée dans le cas de GII double canal. Quant aux 17,6 % des autres cas, la détérioration neurologique peut s'expliquer par le matériel lui-même. CONCLUSION: Une forme de détérioration neurologique a accompagné 27,4 % des remplacements de GII chez des patients atteints de MP et nécessitant des séances de SCP pour soulager leurs douleurs chroniques. Environ 82,4 % de ces cas seraient évitables en surveillant attentivement les paramètres de stimulation pour qu'ils correspondent ainsi aux niveaux d'énergie électrique totale produits avant remplacement.

Neurophysiology and neurochemistry of corticobasal syndrome.

Corticobasal syndrome is a rare neurodegenerative disorder, which presents with a progressive, asymmetrical, akinetic rigid syndrome and early cortical signs. However, clinical, pathological, and electrophysiological heterogeneity makes the understanding of this syndrome challenging. Corticobasal syndrome can have various pathological substrates including corticobasal degeneration, Alzheimer's disease, Fronto-temporal degeneration with TDP inclusions, Creutzfeldt-Jakob disease, and progressive supranuclear palsy (PSP). Furthermore, tools such as transcranial magnetic stimulation (TMS) and functional neuroimaging techniques like PET and SPECT have not been adequately used to supplement the clinico-pathological heterogeneity. TMS studies in CBS have revealed changes in cortical excitability and transcortical inhibition. Despite the availability of more than 2 decades, its potential in CBS has not been fully utilized in studying the cortical plasticity and effect of Levodopa on central neurophysiology. PET and SPECT studies in CBS have shown abnormalities in regional glucose metabolism, asymmetrical involvement of presynaptic dopaminergic system, and ascending cholinergic connections to the cortex. While most studies have shown normal D2 receptor-binding activity in striatum of CBS cases, the results have not been unanimous. Functional neuroimaging and TMS studies in CBS have shown the involvement of GABAergic, muscarinic, and dopaminergic systems. In this review, we aim to provide the current state of understanding of central neurophysiology and neurochemistry of CBS using TMS and functional neuroimaging techniques. We also highlight the heterogeneous nature of this disorder and the existing knowledge gaps.

Memantine-induced Myoclonus in a Patient with Alzheimer Disease.

BACKGROUND: Myoclonus can be a clinical manifestation of numerous neurodegenerative disorders and an adverse drug reaction to medications used in their treatment. CASE REPORT: Herein, we report memantine-induced myoclonus in a patient with Alzheimer disease. The myoclonus seen in our patient was generalized (proximal limbs and trunk), present at rest and with action, and stimulus sensitive. A structured evaluation with the Unified Myoclonus Rating Scale showed that the myoclonus had no significant effect on functional capacity. After discontinuation of memantine, myoclonus slowly resolved over the course of several weeks. DISCUSSION: Memantine may cause myoclonus in susceptible individuals.

Valproate therapy exacerbating intermediate phenotype of methylmalonic aciduria.

A, 11-year-old male, with delayed milestones after the age of 6 months with recurrent myoclonus and generalized tonic-clonic seizures had clinical worsening after institution of valproate, was detected to have elevated serum lactate level and marked methyl malonic aciduria. Patient had remarkable improvement following withdrawal of valproate and substitution of hydroxocobalamin.

Refractory status epilepticus complicated by drug-induced involuntary movements.

New onset refractory status epilepticus (NORSE) is a neurological emergency and difficult to treat condition. We report a case of involuntary movements resulting from thiopentone sodium infusion during the management of refractory status epilepticus. A young woman was admitted with fever and NORSE in the neurology intensive care unit. In addition to supportive measures, she was treated with intravenous lorazepam, phenytoin sodium, sodium valproate, midazolam and thiopentone sodium. While on thiopentone sodium, she developed involuntary twitches involving her upper limbs and face with EEG showing no evidence of ongoing status epilepticus. Because of the temporal relationship with thiopentone infusion, we tapered the dose of thiopentone sodium, which resulted in the disappearance of the movements. The patient recovered well with no recurrence of the seizures during the hospital stay.

Semiologic classification of psychogenic non epileptic seizures (PNES) based on video EEG analysis: do we need new classification systems?

PURPOSE: Different studies have described useful signs to diagnose psychogenic non-epileptic seizure (PNES). A few authors have tried to describe the semiologic groups among PNES patients; each group consisting of combination of features. But there is no uniformity of nomenclature among these studies. Our aim was to find out whether the objective classification system proposed by Hubsch et al. was useful and adequate to classify PNES patient population from South India. METHODS: We retrospectively analyzed medical records and video EEG monitoring data of patients, recorded during 3 year period from June 2010 to July 2013. We observed the semiologic features of each PNES episode and tried to group them strictly adhering to Hubsch et al. classification. Minor modifications were made to include patients who were left unclassified. RESULTS: A total of 65 patients were diagnosed to have PNES during this period, out of which 11 patients were excluded due to inadequate data. We could classify 42(77.77%) patients without modifying the defining criteria of the Hubsch et al. groups. With minor modification we could classify 94.96% patients. The modified groups with patient distribution are as follows: Class 1--dystonic attacks with primitive gestural activities [3(5.6%)]. Class 2 ­ paucikinetic attacks with or without preserved responsiveness [5(9.3%)]. Class 3--pseudosyncope with or without hyperventilation [21(38.9%)]. Class 4--hyperkinetic prolonged attacks with hyperventilation, involvement of limbs and/or trunk [14(25.9%)]. Class 5--axial dystonic attacks [8(14.8%)]. Class 6--unclassified type [3(5.6%)]. CONCLUSION: This study demonstrates that the Hubsch's classification with minor modifications is useful and adequate to classify PNES patients from South India.

Transient bradycardia induced by thiopentone sodium: a unique challenge in the management of refractory status epilepticus.

Thiopentone sodium is one of the important drugs in the armamentarium for terminating refractory status epilepticus, a neurological emergency. We report a case of thiopentone-related bradycardia during the management of the new onset refractory status epilepticus in a young man, which was circumvented by prophylactic insertion of temporary pacemaker while thiopentone infusion was continued. A systematic approach was employed to manage the status epilepticus, including infusion of thiamine and glucose followed by antiepileptic drugs. The patient was ventilated and infused with lorazepam, phenytoin, sodium valproate, levetiracetam and midazolam followed by thiopentone sodium. With the introduction of thiopentone the seizures could be controlled but the patient developed severe bradycardia and junctional rhythm. The bradycardia disappeared when thiopentone was withdrawn and reappeared when the drug was reintroduced. Propofol infusion was tried with no respite in seizures. Later thiopentone sodium was reintroduced after inserting temporary cardiac pacemaker. Seizure was controlled and patient was weaned off the ventilator.