Clinical and Electrophysiological Characterization of Essential Tremor in 18 Children and Adolescents.

Background: Essential tremor (ET) is considered the most frequent abnormal movement in the general population, with childhood onset in 5 to 30% of the patients. Methods: A multicenter, descriptive cross-sectional study enrolled patients ⩽18 years with a definite diagnosis of ET according to the International Parkinson and Movement Disorders Society criteria. Demographic data, clinical and electrophysiological characteristics of the tremor, neurological examination and impact on quality of life were collected. Results: 9 males and 9 females were included (mean age of 13.9 years). Tremor was characterized by : upper limb onset at a mean age of 6.5 years; at enrollment, upper limbs localization, and involvement of an additional body region in 28% of the patients; kinetic tremor in all of the patients combined with postural tremor in 17 and rest tremor in 3; tremor mean frequency of 7.6 Hz, mean burst duration of 82.7 ms; identification of mild myoclonic jerks on the polymyographic recordings in 7 patients; altered quality of life with worse emotional outcomes in girls and when a disease duration >5 years was suggested. Discussion: Childhood-onset ET is associated with delayed diagnosis and remarkable functional impact. Electromyographic identification of additional mild myoclonus is a new finding whose significance is discussed. Highlights: ET onset involved upper limbs and at inclusion, 28% of the patients exhibited involvement of an additional body region.ET impacted quality of life for all patients.Girls and patients affected for >5 years reported worse emotional outcomes.Mild myoclonic jerks were identified on 7/17 polymyographic recordings.

Deep brain stimulation in a patient with progressive myoclonic epilepsy and ataxia due to potassium channel mutation (MEAK). A case report and review of the literature.

Progressive myoclonic epilepsy (PME) is characterized by prominent myoclonus, generalized tonic-clonic seizures, and less often focal, tonic, or absence seizures. The KCNC1 mutation is responsible for specific clinical phenotype of PME which has been defined as myoclonic epilepsy and ataxia due to potassium channel mutation (MEAK). We present a case of a 44 years-old male patient with genetically proven MEAK who underwent subthalamic nucleus/substantia nigra (STN/SNr) deep brain stimulation (DBS) for his pharmacological-refractory myoclonus and drug-resistant epilepsy (DRE). Since the age of 4-5 years, the patient had been suffering from intention tremor, and later the myoclonic jerks, ataxia involving the upper limbs and walking difficulties worsened. The first bilateral tonic-clonic seizure (BTCS) occurred at the age of 22. The patient agreed to staged bilateral implantation of DBS electrodes placed in the STN/SNr region. The follow-up lasts more than 24 months. The myoclonic jerks assessed by Unified Myoclonus Rating Scale (UMRS) were reduced by nearly 70 % and BTCS was completely abolished. The patient's ataxia and dysarthria did not improve. Early diagnosis with genetic testing may significantly help in counseling patients with PME and enables to undertake the surgical approach targeting the STN/SNr.

Pyridoxine Deficiency and Neurologic Dysfunction: An Unlikely Association.

Pyridoxine deficiency is a prevalent condition in the United States that primarily affects patients with alcohol use disorder. The presentation of this condition is very nonspecific and commonly presents with a constellation of symptoms including peripheral neuropathy, stomatitis, dermatitis, confusion, depression, encephalopathy, and seizures. Over half of these patients have associated alcohol use disorder, which causes pyridoxine deficiency due to the breakdown of pyridoxal phosphate during ethanol metabolism in the liver. As an important cofactor in the synthesis of γ-aminobutyric acid (GABA), deficient levels of pyridoxine may lower the seizure threshold due to reduced GABA-mediated inhibition. This case details a 57-year-old male with chronic alcoholism and a history of seizures who developed episodes of myoclonic jerks, tremors, anxiety, and neuropathy whose symptoms persisted even while on anti-epileptic medication. He was found to have pyridoxine deficiency and had full resolution of symptoms shortly after the administration of vitamin B6 supplementation. Pyridoxine deficiency may lead to severe neurologic disorders such as encephalopathy and seizures. Hence, it is important to consider pyridoxine deficiency in the workup of neurologic complaints, especially in high-risk patients.

Low glycemic index therapy in children with sub-acute sclerosing panencephalitis (SSPE): an experience from a measles-endemic country.

Introduction: Sub-acute sclerosing panencephalitis (SSPE) is a chronic, progressive neurodegenerative disorder, commonly seen in measles-endemic countries leading to progressive neuronal loss and death. Currently, there is no proven cure for this devastating disease. We started a low glycemic index therapy (LGIT) in children with SSPE using the same principle as per its role in intractable epilepsy. Methodology: Low glycemic index diet was started in children with a confirmed diagnosis of SSPE based on Dyken's criteria. All children were then classified into four stages according to disease progression. The response to diet was evaluated by improvement in their myoclonic jerks, motor activities, and changes in their stage of the disease. Results: A total of 12 children were enrolled. The mean age was 6.65 years (range 3.3-10 years), with a male-to-female ratio of 2:1. Five children were at stage IV, five were at stage III, and two were at stage II at the start of the diet. Nine (75%) children showed improvement in their stage of illness. Of three children who were at stage IV at the initiation of the diet, one improved to stage II and two to stage III. Four children at stage III reverted to stage II. Two children initiated at stage II went into total remission. Seven (58.3%) children showed a >50% reduction in myoclonic jerks with three (25%) having a 100% reduction. Three (25%) children died due to pneumonia. Conclusion: LGIT may play an effective role in the management of SSPE and gives hope to families having children with this potentially life-threatening disease.

Anticonvulsant potential of Grewia tiliaefolia in pentylenetetrazole induced epilepsy: insights from in vivo and in silico studies.

Epilepsy, a chronic neurological condition, impacts millions of individuals globally and remains a significant contributor to both illness and mortality. Available antiepileptic drugs have serious side effects which warrants to explore different medicinal plants used for the management of epilepsy reported in Traditional Indian Medicinal System (TIMS). Therefore, we explored the antiepileptic potential of the Grewia tiliaefolia (Tiliaeceae) which is known for its neuroprotective properties. Aerial parts of G. tiliaefolia were subjected to extraction with increasing order of polarity viz. hexane, chloroform and methanol. Antioxidant potential of hexane, chloroform and methanol extracts of G. tiliaefolia was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay, total antioxidant capacity (TAC) assay, reducing power assay (RPA) and DNA nicking assay. Additionally, quantitative antioxidant assays were also conducted to quantify total phenolic (TPC) and total flavonoid content (TFC). As revealed by in vitro assays, methanol extract was found to contain more phenolic content. Hence, the methanol extract was further explored for its anticonvulsant potential in pentylenetetrazole (PTZ) induced acute seizures in mice. The methanol extract (400 mg/kg) significantly increased the latency to occurrence of myoclonic jerks and generalized tonic clonic seizures (GTCS). Additionally, it also reduced duration and seizure severity score associated with GTCS. The Grewia tiliaefolia methanol extract was further screened by Ultra High-Performance Liquid Chromatography (UHPLC) for presence of polyphenolic compounds, among which gallic acid and kaempferol were present in higher amount and were further analysed by in silico study to predict their possible binding sites and type of interactions these compounds show with gamma amino butyric acid (GABA) receptor and glutamate α amino-3- hydroxyl-5-methyl-4-isoxazolepropionic acid (Glu-AMPA) receptor. It was revealed that gallic acid and kaempferol had shown agonistic interaction for GABA receptor and antagonistic interaction for Glu-AMPA receptor. We concluded that G. tiliaefolia showed anticonvulsant potential possibly because of gallic acid and kaempferol possibly mediated through GABA and Glu-AMPA receptor.

Myoclonic Jerks and Ataxia: A Case of Rare Neurological Side Effects of Amiodarone.

We present the case of an 85-year-old man with a known medical history of recurrent ventricular arrhythmia and paroxysmal atrial fibrillation who was started on an amiodarone loading dose four days before presenting with tremors and balance impairment. Amiodarone's adverse effects in various systems have been well studied, although this is not the case with neurotoxic side effects. In this article, we discuss the neurotoxic side effects caused by amiodarone and the importance of a complete physical examination when starting this medication for supraventricular and ventricular arrhythmias.

Recurrent convulsive syncope misdiagnosed as seizures due to a diaphragmatic hernia.

Differential diagnosis of seizures and convulsive syncope may be challenging in clinical practice. Furthermore, a misleading diagnosis of epilepsy may be detrimental for the patient as it often implies an over-prescription and an over-use of antiepileptic drugs which can cause adverse reactions. Moreover, a wrong diagnosis also causes distress to the patient with the risk of performing plenty of investigations without any benefits on the symptoms. In this case, we present a 57-year-old patient suffering from recurrent convulsive syncope over the last 7 years for which he underwent several cardiological and neurological tests and took plenty of antiepileptic drugs without any benefits on his convulsive episodes with loss of consciousness. During hospitalization, a chest X-ray was performed revealing an unknown diaphragmatic hernia with eventration of the transverse colon in the right hemitorax and mild cardiac compression. The patient underwent laparotomic surgery and diaphragmatic reconstruction with complete recovery. After 6-month follow-up, the patient no longer had episodes of convulsive syncope.

Focal status and acute encephalopathy in a 13-year-old boy with de novo DNM1L mutation: Video-polygraphic pattern and clues for differential diagnosis.

BACKGROUND: Pathogenic variants in the dynamin 1 like gene are related to abnormal mitochondrial dynamics and distributions and are associated to variable clinical phenotypes. A few patients harboring the p.Arg403Cys missense variant appears to be different from the classical, more severe phenotypes, showing sudden onset of drug resistant seizures after a previously normal or slightly delayed development. CASE REPORT: We report on a boy with abrupt onset of focal status and coma at the age of 13, initially treated as autoimmune encephalitis, with final diagnosis of de novo missense p.Arg403Cys variant in the DNM1L gene. DISCUSSION: We compare his clinical, electrophysiological, biochemical, neuroradiological and histopathological picture to the rare cases reported to date and provide diagnostic clues that can help clinicians in differentiate p.Arg403Cys-related phenotype from that of immune-mediated encephalopathies. CONCLUSION: The clinical picture related to p.Arg403Cys mutations should be considered alongside acquired pathologies in the differential diagnosis of young patients with focal refractory epilepsy and encephalopathy, also occurring during late childhood or adolescence. Prompt genetic testing allows to avoid unnecessary treatments and procedures and to better define the prognosis and management strategies.

A Case Report of Myoclonus-Dystonia with Isolated Myoclonus Phenotype and Novel Mutation Successfully Treated with Deep Brain Stimulation.

INTRODUCTION: Myoclonus-dystonia is an inherited disorder characterized by a combination of myoclonic jerks and dystonia. Mutations in the epsilon-sarcoglycan gene (SGCE) represent the main known genetic cause. In the last few years, deep brain stimulation (DBS) has shown significant promise in treating these patients. There is only one report in the literature of a patient with positive SGCE mutation and isolated myoclonus phenotype who has been successfully treated with DBS. CASE PRESENTATION: We present a case of a 16-year-old young man with a history of quick jerks since childhood. They progressed gradually over the years involving the entire body and interfering with most of his daily activities. He had no dystonia. Genetic testing identified a single base deletion in exon 3 of the SGCE gene, considered very likely pathogenic. After unsuccessfully trying several oral medications, he underwent DBS of the globus pallidus internus (GPi). His Unified Myoclonus Rating Scale score during rest and with action improved by 92.8% and 82.6%, respectively. DISCUSSION: The striking effect of DBS on myoclonic jerks confirms the superior benefit of DBS over oral medications. Further study is needed to determine the role of mutation status in predicting DBS response, especially considering that myoclonus-dystonia is genetically heterogeneous. CONCLUSION: Our case confirms the poor response to oral medications and supports the use of GPi DBS for patients with genetically confirmed myoclonus-dystonia and isolated-myoclonus phenotype. In addition, our case represents familial myoclonus-dystonia due to a novel SGCE mutation.

Subacute Sclerosing Panencephalitis Causing Rapidly Progressive Dementia and Myoclonic Jerks in a Sexagenarian Woman.

Background: Subacute sclerosing panencephalitis (SSPE) is a disease of childhood and adolescence, but can affect adults. Rapidly progressive cognitive decline, seizures including myoclonic jerks, spasticity, ataxia, visual disturbances, and incontinence are typical manifestations. Case report: A 62-year-old woman who presented with rapidly progressive dementia and myoclonus was diagnosed with SSPE. There was resolution of the movement disorder with clonazepam and valproic acid treatment and some amelioration of cognitive decline after 3 months of therapy with interferon alfa and isoprinosine. Discussion: With the recent rise in measles cases worldwide, any increased incidence of SSPE would require vigilance for early interventions.

Infantile Spasms: Clinical profile and treatment outcomes.

BACKGROUND AND OBJECTIVE: Infantile spasm (IS) is one of the severe epileptic encephalopathies which affect children in early two years of life. Our objective was to determine the clinical profile, etiology and outcome of treatment in children with infantile spasms attending tertiary care hospital at Karachi, Pakistan. METHODS: This is retrospective study of 36 patients out of 94 registered as IS, aged three months to two years, managed and followed up at Aga Khan University Hospital, Karachi, from 2010 to 2015. Data of all children with IS was collected from case record. Details including clinical observations, lab investigations, anti-epileptic medications and treatment outcome was collected and analyzed. Patients who received treatment for six weeks to document response were included. The treatment response was categorized as complete response, partial response (>50% improvement) and no response. Data was analyzed on SPSS using descriptive statistics. RESULTS: Thirty- six patients (38.29%) with IS fulfilled eligibility criteria. The mean ± SD age at presentation was 4.6±2.1 months. Male to female ratio was 2:1. Consanguinity and developmental motor delay was observed in 66.6% and 89% respectively. Symptomatic etiology was predominant (61%) and hypoxic ischemic insult (32%) was the commonest underlying cause. EEG and MRI were diagnostic tools whereas metabolic studies were not helpful. Multiple antiepileptic drugs were used for seizure control and vigabatrin was the most frequently used (88%) drug. Short term treatment response was not different in idiopathic or symptomatic infantile spasms. CONCLUSION: Majority of patients had symptomatic infantile spasms and generalized tonic clonic along with myoclonic jerks were predominant seizure types. EEG and MRI were diagnostic in most of cases. Multiple AEDs were required to control seizures and VGB was most common drug (88%) used. Treatment outcome was not different in idiopathic and symptomatic groups.

Myoclonic Jerks and Schizophreniform Syndrome: Case Report and Literature Review.

Background: Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological, or degenerative). Secondary epileptic explanatory approaches have often been discussed in the past, due to the high rates of electroencephalography (EEG) alterations in patients with schizophrenia. In particular, temporal lobe epilepsy is known to be associated with schizophreniform symptoms in well-described constellations. In the literature, juvenile myoclonic epilepsy has been linked to emotionally unstable personality traits, depression, anxiety, and executive dysfunction; however, the association with schizophrenia is largely unclear. Case presentation: We present the case of a 28-year-old male student suffering from mild myoclonic jerks, mainly of the upper limbs, as well as a predominant paranoid-hallucinatory syndrome with attention deficits, problems with working memory, depressive-flat mood, reduced energy, fast stimulus satiation, delusional and audible thoughts, tactile hallucinations, thought inspirations, and severe sleep disturbances. Cerebral magnetic resonance imaging and cerebrospinal fluid analyses revealed no relevant abnormalities. The routine EEG and the first EEG after sleep deprivation (under treatment with oxazepam) also returned normal findings. Video telemetry over one night, which included a partial sleep-deprivation EEG, displayed short generalized spike-wave complexes and polyspikes, associated with myoclonic jerks, after waking in the morning. Video-EEG monitoring over 5 days showed over 100 myoclonic jerks of the upper limbs, frequently with generalized spike-wave complexes with left or right accentuation. Therefore, we diagnosed juvenile myoclonic epilepsy. Discussion: This case report illustrates the importance of extended EEG diagnostics in patients with schizophreniform syndromes and myoclonic jerks. The schizophreniform symptoms in the framework of epileptiform EEG activity can be interpreted as a (para)epileptic mechanism due to local area network inhibition (LANI). Following the LANI hypothesis, paranoid hallucinatory symptoms are not due to primary excitatory activity (as myoclonic jerks are) but rather to the secondary process of hyperinhibition triggered by epileptic activity. Identifying subgroups of schizophreniform patients with comorbid epilepsy is important because of the potential benefits of optimized pharmacological treatment.

Improving neurophysiological biomarkers for functional myoclonic movements.

INTRODUCTION: Differentiating between functional jerks (FJ) and organic myoclonus can be challenging. At present, the only advanced diagnostic biomarker to support FJ is the Bereitschaftspotential (BP). However, its sensitivity is limited and its evaluation subjective. Recently, event related desynchronisation in the broad beta range (13-45 Hz) prior to functional generalised axial (propriospinal) myoclonus was reported as a possible complementary diagnostic marker for FJ. Here we study the value of ERD together with a quantified BP in clinical practice. METHODS: Twenty-nine patients with FJ and 16 patients with cortical myoclonus (CM) were included. Jerk-locked back-averaging for determination of the 'classical' and quantified BP, and time-frequency decomposition for the event related desynchronisation (ERD) were performed. Diagnostic gain, sensitivity and specificity were obtained for individual and combined techniques. RESULTS: We detected a classical BP in 14/29, a quantitative BP in 15/29 and an ERD in 18/29 patients. At group level we demonstrate that ERD in the broad beta band preceding a jerk has significantly higher amplitude in FJ compared to CM (respectively -0.14 ± 0.13 and +0.04 ± 0.09 (p < 0.001)). Adding ERD to the classical BP achieved an additional diagnostic gain of 53%. Furthermore, when combining ERD with quantified and classical BP, an additional diagnostic gain of 71% was achieved without loss of specificity. CONCLUSION: Based on the current findings we propose to the use of combined beta ERD assessment and quantitative BP analyses in patients with a clinical suspicion for all types of FJ with a negative classical BP.

A Case of Early Onset Subacute Sclerosing Panencephalitis Presented as Juvenile Myoclonic Epilepsy.

A 7.5 years girl presented with myoclonic jerks with prolonged duration coming progressively at shorter intervals for last six moinths. There was declining academic performances. The dystonic, dyskinetic movements and ataxia were there for last three months. The stages were progressing too rapidly. IgG antibody titre to measles virus was found to be positive with EEG changes which confirms diagnosis. SSPE at so early age with atypical presentation is unique in this indexed case.

Update on Pharmacological Treatment of Progressive Myoclonus Epilepsies.

BACKGROUND: Progressive myoclonus epilepsies (PMEs) are a group of rare inherited diseases featuring a combination of myoclonus, seizures and variable degree of cognitive impairment. Despite extensive investigations, a large number of PMEs remain undiagnosed. In this review, we focus on the current pharmacological approach to PMEs. METHODS: References were mainly identified through PubMed search until February 2017 and backtracking of references in pertinent studies. RESULTS: The majority of available data on the efficacy of antiepileptic medications in PMEs are primarily anecdotal or observational, based on individual responses in small series. Valproic acid is the drug of choice, except for PMEs due to mitochondrial diseases. Levetiracetam and clonazepam should be considered as the first add-on treatment. Zonisamide and perampanel represent promising alternatives. Phenobarbital and primidone should be reserved to patients with resistant disabling myoclonus or seizures. Lamotrigine should be used with caution due to its unpredictable effect on myoclonus. Avoidance of drugs known to aggravate myoclonus and seizures, such as carbamazepine and phenytoin, is paramount. Psychiatric (in particular depression) and other comorbidities need to be adequately managed. Although a 3- to 4-drug regimen is often necessary to control seizures and myoclonus, particular care should be paid to avoid excessive pharmacological load and neurotoxic side effects. Target therapy is possible only for a minority of PMEs. CONCLUSIONS: Overall, the treatment of PMEs remains symptomatic (i.e. pharmacological treatment of seizures and myoclonus). Further dissection of the genetic background of the different PMEs might hopefully help in the future with individualised treatment options.

From dizziness to severe ataxia and dysarthria: New cases of anti-Ca/ARHGAP26 autoantibody-associated cerebellar ataxia suggest a broad clinical spectrum.

In 2010, a novel anti-neuronal autoantibody, termed anti-Ca, was described in a patient with subacute cerebellar ataxia, and Rho GTPase-activating protein 26 (ARHGAP26) was identified as the target antigen. Recently, three additional cases of anti-Ca-positive cerebellar ataxia have been published. In addition to ataxia, cognitive decline and depression have been observed in some patients. Here, we report two new cases of anti-Ca-associated autoimmune cerebellar ataxia. Patient 1 presented with dizziness and acute yet mild limb and gait ataxia. Symptoms stabilized with long-term oral corticosteroid therapy but transiently worsened when steroids were tapered. Interestingly, both initial occurrence and worsening of the patient's neurological symptoms after steroid withdrawal were accompanied by spontaneous cutaneous hematomas. Patient 2 initially presented with an increased startle response and myoclonic jerks, and subsequently developed severe limb and gait ataxia, dysarthria, oculomotor disturbances, head and voice tremor, dysphagia, cognitive symptoms and depression. Steroid treatment was started five years after disease onset. The symptoms then responded only poorly to corticosteroids. At most recent follow-up, 19 years after disease onset, the patient was wheelchair-bound. These cases extend the clinical spectrum associated with anti-ARHGAP26 autoimmunity and suggest that early treatment may be important in patients with this rare syndrome.

Heat induced temperature dysregulation and seizures in Dravet Syndrome/GEFS+ Gabrg2+/Q390X mice.

It has been established that febrile seizures and its extended syndromes like generalized epilepsy with febrile seizures (FS) plus (GEFS+) and Dravet syndrome have been associated with mutations especially in SCN1A and GABRG2 genes. In patients, the onset of FS is likely due to the combined effect of temperature and inflammation in genetically vulnerable individuals because fever is often associated with infection. Much effort has been spent to understand the mechanisms underlying fever induction of seizures. In addition to the role of cytokines in FS, previous studies in Scn1a+/- knockout mice, a model of Dravet syndrome, indicated that temperature elevation alone could result in seizure generation, and the effect of elevated temperature inducing seizures was age-dependent. Here, we report the thermal effect in a different mouse model of Dravet syndrome, the Gabrg2+/Q390X knockin mouse. We demonstrated age-dependent dysregulated temperature control and that temperature elevation produced myoclonic jerks, generalized tonic clonic seizures (GTCSs) and heightened anxiety-like symptoms in Gabrg2+/Q390X mice. The study indicated that regardless of other inflammatory factors, brief heat alone increased brain excitability and induced multiple types of seizures in Gabrg2+/Q390X mice, suggesting that mutations like GABRG2(Q390X) may alter brain thermal regulation and precipitate seizures during temperature elevations.

A Quandary of Cuprum - Wilson's Disease Disguising as Progressive Myoclonic Epilepsy.

Although metals are indispensable for the production of articles in our daily usage, the deposition of these metals in human tissue is known to cause disease. However, it is not always the ingestion of abnormal amounts of lead, iron, or copper that makes our tissues morbid; our hereditary and metabolic issues are to be blamed as well. Wilson's disease is one such hereditary disease that creates chaos in tissues, usually the brain and liver, via deposition of abnormal amounts of copper in them. While Wilson's disease almost seems to bring a picture of a young patient with dystonia and other extrapyramidal symptoms in our imagination, seizures are very uncommon in this disorder. Non-stimulus-sensitive myoclonic jerks along with cognitive decline as the initial presentation of this disease have never been reported until now. In fact, such a presentation would make the neurologist believe that the patient has some type of progressive myoclonic epilepsy (PME), thus, creating a dilemma. We report two such dilemmatic cases of Wilson's disease that disguised as PME.

Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis.

OBJECTIVES: Subacute sclerosing panencephalitis (SSPE) is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage. METHODS AND RESULTS: Heterogeneity of imaging findings in SSPE is not very uncommon. But pial and gyral enhancements are very rarely noticed. Significant asymmetric onset as well as pial-gyral enhancements is not reported. Herein we present a case of 16 years adolescent of SSPE having remarkable asymmetric pial-gyral enhancements, which were misinterpreted as tubercular infection. CONCLUSION: Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case.