Treatable Neurological Disorder Research Articles

Role of imaging in craniovertebral junction abnormalities

Background: Craniovertebral junction (CVJ) abnormalities constitute an important group of treatable neurological disorders with diagnostic dilemma. Their precise diagnosis and pre-treatment evaluation significantly affects prognosis and quality of life of patients. Aims: To localize, describe and characterize craniovertebral junction abnormalities, arrange frequently detected CVJ pathologic imaging findings and to emphasize clinical implications to improve our radiological report. Materials and methods: A Cross sectional study done for 24 months in 50 patients of all age groups with clinical suspicion of CVJ abnormalities.Results: In the acquired CVJ abnormality Trauma is the most common etiology(n=15) followed by Tuberculosis(n=4), Rheumatoid arthritis(n=3), Tumors(n=2). Most common age group involved was 2nd decade with male predominance. Most commonly presenting symptom is weakness of limbs followed by neck pain. Most common imaging abnormality is cervicomedullary junction compression and atlanto axial dislocation. ACM I and Syringomyelia are the commonest neural anomalies associated with bony CVJ anomalies. Most common congenital anomalies are atlanto axial dislocation followed by basilar invagination. Only one patient had syndromic association which was Klippel-feil syndrome. The commonest injuries involving the CVJ were odontoid fracture predominantly type II and the commonest combination of injury was C1 with odontoid fracture.

Spectrum of non-traumatic craniovertebral junction disorders

Introduction: Craniovertebral junction is the “zone of transition” between the skull and cervical spine so its detailed discussion is lacking in so many standard textbooks addressing these regions. These anomalies are especially common in the Indian subcontinent. Accurate diagnosis, probable aetiology and pre-treatment evaluation considerably affect the prognosis of patients. The aim of this study was to classify various Craniovertebral junction disorders according to their aetiology and to correlate the imaging findings with the clinical profile of the patients and histopathology whenever possible.
 Methods: This prospective observational study was done in our department over the period of one year from August 2016 to July 2017. 57 North Indian patients from all age groups and both sex, who had imaging features suggesting craniovertebral junction pathology were selected for the study.
 Results: Our study group comprised 34 males and 23 females with a male to female ratio of 1.47: 1. The most common age group was 11-20 years and the most common aetiology being developmental followed by infective, autoimmune and inflammatory disorders.
 Conclusions: CVJ abnormalities are a group of treatable neurological disorders, and are approached with much caution by clinicians. Thus, it is crucial that radiologists should be able to make a precise diagnosis, categorize them into etiological groups, and give precise anatomical information on MDCT and/or MRI, as this information ultimately helps determine the management of such abnormalities and their prognosis.

Clinical Application of Whole Exome Sequencing to Identify Rare but Remediable Neurologic Disorders.

Background: The aim of this study was to describe the application of whole exome sequencing (WES) in the accurate genetic diagnosis and personalized treatment of extremely rare neurogenetic disorders. Methods: From 2017 to 2019, children with neurodevelopmental symptoms were evaluated using WES in the pediatric neurology clinic and medical genetics center. The clinical presentation, laboratory findings including the genetic results from WES, and diagnosis-based treatment and outcomes of the four patients are discussed. Results: A total of 376 children with neurodevelopmental symptom were evaluated by WES, and four patients (1.1%) were diagnosed with treatable neurologic disorders. Patient 1 (Pt 1) showed global muscle hypotonia, dysmorphic facial features, and multiple anomalies beginning in the perinatal period. Pt 1 was diagnosed with congenital myasthenic syndrome 22 of PREPL deficiency. Pt 2 presented with hypotonia and developmental arrest and was diagnosed with autosomal recessive dopa-responsive dystonia due to TH deficiency. Pt 3, who suffered from intractable epilepsy and progressive cognitive decline, was diagnosed with epileptic encephalopathy 47 with a heterozygous FGF12 mutation. Pt 4 presented with motor delay and episodic ataxia and was diagnosed with episodic ataxia type II (heterozygous CACNA1A mutation). The patients’ major neurologic symptoms were remarkably relieved with pyridostigmine (Pt 1), levodopa (Pt 2), sodium channel blocker (Pt 3), and acetazolamide (Pt 4), and most patients regained developmental milestones in the follow-up period (0.4 to 3 years). Conclusions: The early application of WES helps in the identification of extremely rare genetic diseases, for which effective treatment modalities exist. Ultimately, WES resulted in optimal clinical outcomes of affected patients.

Embryological considerations and evaluation of congenital anomalies of craniovertebral junction: A single-center experience

Objectives:Craniovertebral junction (CVJ) abnormalities constitute a group of treatable neurological disorders, especially in the Indian subcontinent. Thus, it is essential that clinicians should be able to make a precise diagnosis of abnormalities and rule out important mimickers on multidetector computed tomography (MDCT) as this information ultimately helps determine the management, prognosis, and quality of life of patients. CVJ is the most complex part of the cervical region. Congenital malformations of this region can cause serious neurological deficit and require a surgical intervention. The present study was undertaken to know the embryological basis of the CVJ and to identify commonly observed congenital CVJ abnormalities, their frequency, and mode of presentation.Materials and Methods:Diagnosed cases of CVJ anomalies on dynamic MDCT head were reviewed at a tertiary care center between January 2014 to December 2019. Type of anomaly, clinical presentation, and associated malformations were recorded. Different types of variations were expressed in terms of percentage.Results:Congenital anomalies were seen in 42 cases. Fifteen types of anomalies were detected. Anomalies were either singly or in combination. The CVJ anomalies were more common in young adults (28%), almost equal in both sexes. The most common anomaly was basilar invagination (52.3%), followed by atlanto-occipital assimilation (33.3%), and Arnold–Chiari malformation is the most common soft tissue anomaly. In fourteen cases, additional anomalies of other vertebrae were present. The most common symptoms were weakness of extremities, neck pain, paresthesia, torticollis, and gait disturbances. About 28 patients got improved, 8 patients had residual deficit as that of preoperative status, and 4 patients got deteriorated after surgery, at 1-month follow-up. About 34 patients had improved, 5 remained static, and 3 patients got worsened at the end of 3-month follow-up. About 37 patients had improved, 4 patients remained static, and 2 patients got deteriorated at 6 months of follow-up. The patients with increased atlantodens interval 3–5 mm showed 77% improvement after surgery.Conclusion:Congenital CVJ anomalies, though rare, are fatal. CVJ abnormalities constitute an important group of treatable neurological disorders with diagnostic dilemma. The atlantodental interval is the most important preoperative prognostic marker. Dynamic CT imaging can provide additional useful information to the diagnosis of CVJ instability. To prevent long-term neurological problems, early diagnosis and treatment of congenital bony CVJ anomalies is important.

Idiopathic intracranial hypertension in a case of mycoplasma pneumonia

Idiopathic intracranial hypertension in a case of mycoplasma pneumonia - IJN- Print ISSN No: - 2581-8236 Online ISSN No:- 2581-916X Article DOI No:- 10.18231/j.ijn.2020.045, IP Indian Journal of Neurosciences-IP Indian J Neurosci

Epilepsy over the centuries: a disease survived at the time.

In this study, we have made a historical review of epilepsy through the centuries, from pre-Christian era to the present time. The epileptic was examined by Hippocrates, the first to recognize epilepsy as a disease and not as a supernatural manifestation called Morbus Sacer. The dark years of the Middle Ages were the worst for the disease, where the sufferer was even subjected to torture. The period of the Renaissance saw the epileptic isolated from society while the Enlightenment century improved the knowledge about the disease, thanks also to the first autopsies that showed post traumatic neurological lesions. However, some stigmata of the disease that prevented the marriage of epileptics persisted. It was the prelude to the years 1800-1900, characterized by Lombrosian concepts and Nazi convictions. Lombroso included epileptics among delinquents and criminals, identifying them as such on the basis of physical alterations. Nazi racism introduced the concept of eugenics excluding the epileptic from the so-called pure race. Today, epilepsy is considered a treatable neurological disorder. Morbus Sacer belongs to a remote past.

Current Update on Treatment Strategies for Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a surgically treatable neurological disorder of the elderly population that is characterized by abnormal ventricular enlargement due to cerebrospinal fluid (CSF) accumulation and gait disturbance, cognitive impairment, or urinary incontinence. The objective of this review is to present the current diagnostic and treatment approaches for iNPH and to discuss some of the postoperative modalities that complement positive surgical outcomes. Although historically reported patient outcomes following iNPH surgery were dismal and highly variable, recent advances in terms of better understanding of the iNPH disease process, better standardization of iNPH diagnostic and treatment processes arising from the adoption of clinical guidelines for diagnosis, treatment and in research methodologies, and availability of long-term follow-up data, have helped reduce the variations to a much improved 73 to 96% reported good outcomes. With careful evaluation, good patient selection, and advanced surgical techniques, iNPH can be surgically treated to return patients close to their pre-iNPH functional status. Institution of an interdisciplinary effort to rehabilitate patients following surgery may help augment their recovery.

S100A6 Promotes B Lymphocyte Penetration Through the Blood-Brain Barrier in Autoimmune Encephalitis.

Autoimmune encephalitis (AE) is a severe neurological disease. The brain of the AE patient is attacked by a dysregulated immune system, which is caused by the excessive production of autoantibodies against neuronal receptors and synaptic proteins. AE is also characterized by the uncontrolled B lymphocyte infiltration through the blood–brain barrier (BBB) layer, and the investigation of the underlying mechanism involved in this infiltration may facilitate the discovery of novel therapies for AE. However, few AE-related studies have focused on this issue. In this study, we aimed to identify the factors involved in B lymphocyte infiltration in AE. For this purpose, we first enrolled four healthy control and five AE subjects, collecting their serum and/or total white blood cell samples. The white blood cell samples were further used for collecting RNA and DNA. Then, we simulated the in vivo B lymphocyte infiltration with an in vitro leukocyte transendothelial migration model. It turned out that AE serum treatment significantly and specifically promoted B cells to penetrate the BBB endothelial layer without affecting neutrophils. Next, through genome-wide DNA methylation assays on bisulfite-conversion DNA samples, we identified S100A6 and S100A11 as potential hypo-methylated disease genes in the AE samples. Further qPCR assays demonstrated their upregulation in AE samples, reflecting the negative correlations between gene expression and DNA methylation. Finally, recombinant S100A6 protein treatment significantly increased B lymphocyte infiltration through the BBB endothelial layer, which partially recapitulated the effect of AE serum. In summary, by using an in vitro leukocyte transendothelial migration model, we confirmed that S100A6 promoted B lymphocyte to penetrate the BBB endothelial layer, which is similar to the in vivo clinical manifestations of AE. Therefore, further studies on how the S100A6 protein facilitates B lymphocyte infiltration and on whether other factors in serum also contribute to this phenomenon are likely to improve our understanding of AE and hopefully to reveal novel therapeutic targets for this emerging treatable neurological disorder.

Epilepsy Disorders and Treatment Modalities.

Epilepsy disorders are the most common treatable neurological disorders in childhood. Diagnosis and treatment of these disorders has improved over time. Children with epilepsy/seizure disorder are more likely to have or develop mental health and developmental comorbidities such as depression, anxiety, attention deficit hyperactivity disorder, learning disabilities, and developmental delay compared to children without epilepsy/seizure disorder. If seizures can be controlled, quality of life will improve. This article will review the current medical treatment for seizures and epilepsy, including medications, vagus nerve stimulation (VNS), dietary modifications, and surgical intervention.

Treatment and rehabilitation outcomes of children affected with nodding syndrome in Northern Uganda: a descriptive case series.

IntroductionNodding Syndrome (NS) is a neurological disorder affecting children 5-15 years at onset in East Africa. A major criterion for diagnosis is atonic seizure with dorso-ventral “nodding” of the head. Comorbidities include psychological and behavioral abnormalities, malnutrition, cognitive decline, school dropout and other seizure types. We aimed to describe the presentations and rehabilitation outcomes of NS children at Hope for HumaNs (HfH) centre in Gulu from September 2012 to October 2013.MethodsData was obtained from a retrospective review of 32 NS children's medical records at HfH center. Ethical approval was obtained from Gulu University IRB. Data analysis was conducted using WHO AnthroPlus, SPSS and Excel software.ResultsGrowth statistics showed steady improvement over time using local nutrition and multivitamin supplementation. Severe and moderate stunting was reduced from a combined total of 54.8% to 7.7% and 12.8% respectively. Severe and moderate wasting was reduced from 29.1% to 2.6% and 5.1% respectively. Three groups of NS children were identified and compared in the review; Low seizure occurrence averaging <2 seizures/month (28.1%); Moderate averaging 2-4 seizures/month (34.4%) and High averaging >4 seizures/month (37.5%).ConclusionNS is a neurological disorder of unknown etiology. Treatment with regular high quality local nutrition, multivitamin supplementation, anti-seizures, regular follow up and illness prevention; children's seizures can be reduced or stopped completely. The debilitating malnutrition and stunting of NS children in Uganda could be partially independent of the syndrome but attributable to poor nutrition. NS as observed is not “invariably fatal” but rather a treatable neurological disorder.

IgLON5 antibody: Neurological accompaniments and outcomes in 20 patients.

Objective:To describe the phenotypes, treatment response, and outcome of IgLON5 autoimmunity.Methods:Archived serum and CSF specimens from 367 patients known to harbor unclassified antibodies which stained neural synapses diffusely (mimicking amphiphysin-IgG) were reevaluated by indirect immunofluorescence assay (IFA) using a composite of mouse tissues and recombinant IgLON5-transfected cell-based assay (CBA, Euroimmun).Results:Available specimens (serum, 25; CSF, 9) from 26/367 patients (7%) had identical IFA appearance and robust IgLON5 CBA positivity. Clinical information was available for 20/26 patients; 13 were women. Median disease-onset age was 62 years (range, 46–75 years). Most patients had insidious onset and progression of neurological symptoms affecting movement and sleep predominantly. Sleep disorders were sleep-disordered breathing (11) and parasomnias (3). Brainstem disorders were gait instability (14), dysphagia (10), abnormal eye movements (7), respiratory dysfunction (6), ataxia (5), craniocervical dystonia (3), and dysarthria (3). Findings compatible with hyperexcitability included myoclonus (3), cramps (3), fasciculations (2), and exaggerated startle (2). Neuropsychiatric disorders included cognitive dysfunction (6), psychiatric symptoms (5), and seizures (1). Dysautonomia, in 9, affected bladder function (7), gastrointestinal motility (3), thermoregulation (3), and orthostatic tolerance (1). Just 2 patients had coexisting autoimmune disease. Brain MRI findings were nonspecific and CSF was noninflammatory in all tested. Seven of 9 immunotherapy-treated patients improved: 6 of those 7 were stable at last follow-up. Three untreated patients died. Each IgLON5-IgG subclass (1–4) was readily detectable in ≥80% of specimens using CBA.Conclusions:IgLON5-IgG is diagnostic of a potentially treatable neurological disorder, where autoimmune clues are otherwise lacking.

Obravnava novoodkritih bolnikov z miastenijo gravis v regionalni bolnišnici med leti 2003–2013

Background: Myasthenia gravis (MG) is the most common autoimmune disorders of the neuromuscular junction. Advances in intensive care in conjunction with the advent of novel treatments have made MG one of the most treatable neurological disorders. The incidence and prevalence rates of MG have increased over time due to greater disease awareness, better diagnostic methods and ageing of the population. Due to these facts, the number of MG patients evaluated at the secondarylevel regional hospitals has increased. So far, no data on the evaluation of MG in Slovenia have been systematically collected. The aim and scope of this article is to present the analysis of the evaluation of newly diagnosed MG patients at the General hospital of Isola for the time period between 1 January 2003 and 31 December 2013.Methods: We reviewed medical files of MG patients diagnosed at the General hospital of Isola in the above mentioned time period and collected data on patients’ demographic and clinical characteristics in addition to examining their clinical course and treatment outcome.Results: Twenty-nine patients were identified (14 women, 15 men). Te mean age at disease onset was 59.4 ± 21.2 years for women and 56.3 ± 19.8 years for men. In the study population, 58.6 % of the patients were acetylcholine receptor antibody positive. Besides MG, patients most often had thyroid and other chronic diseases. Most patients (68.9 %) presented with extraocular disease symptoms, which progressed to generalized disease in 65 % of cases. Myasthenic crisis occurred in 10.3 % of patients. In 68.9 % of cases, the patients were treated exclusively with symptomatic therapy. Tymectomy was performed in 13.7 % of cases. On treatment, 13.7 % achieved a stable complete remission of MG symptoms, in 55 % the condition substantially improved, in 20.6 % improvement was only partial, and in 6.8 % of patients the condition remained unchanged. The fiveyear mortality of the study population, estimated according to the Kaplan-Meier method was 13.5 %.Conclusions: With the exception of a higher mortality rate, the patients’ characteristics and clinical course of the disease were similar to data reported in other epidemiological studies. The patients’ higher mortality rate was considered to be a consequence of the lack of intensive treatment in patients with myasthenic crisis due to the unawareness of the reversibility of the condition with an adequate treatment.

Olfactory ability in normal pressure hydrocephalus as compared to Alzheimer's disease and healthy controls

ObjectivesNormal pressure hydrocephalus (NPH) is a treatable neurological disorder that appears in older adults, lacks specific diagnostic criteria, and resembles symptoms seen in Alzheimer's disease (AD). Presently, differentiating NPH from AD in the early stages of symptom presentation remains difficult. This study established whether olfactory testing may be useful in this regard. In addition, we determined whether olfactory function of NPH patients differed before and after extended lumbar drainage (ELD), as well as six months after surgical implantation of a ventriculoperitoneal (VP) shunt. Patients and methodsTwenty-two NPH patients (mean age=77.6yrs), 14 age- and gender-matched healthy controls (mean age=79.9yrs), and 7 AD patients (mean age=75.5yrs) were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Eighteen of the 22 NPH patients were also tested following ELD and 8 patients were tested six months following implantation of VP shunt. ResultsPrior to ELD, patients with NPH scored significantly higher on the UPSIT than those with AD [respective means (SDs)=26.9 (7.1) & 14.1 (4.7)]. While the mean NPH score was significantly below that of the matched controls [control mean (SD)=32.7 (6.7)], their test scores were nonetheless within the general normal range, as determined from published normative data (48th percentile). The UPSIT scores did not differ significantly among the three longitudinal time points in the NPH patients. ConclusionOlfactory testing may be useful in differentiating between patients with NPH and patients with AD. Odor identification test scores of NPH patients are not influenced by the release of intracranial pressure via ELD or six months following implantation of a VP shunt.

More than just a headache

Primary headache disorders are some of the most prevalent, disabling and largely treatable neurological disorders, and the associated financial burden is huge; in the UK alone, the cost of headaches is estimated to be about US$10 billion per year. Patricia Luna investigates why, despite global efforts, headache is by far the most under-funded of all neurological disorders.

Steroid hormones in prediction of normal pressure hydrocephalus

Normal pressure hydrocephalus (NPH) is a treatable neurological disorder affecting elderly people with the prevalence increasing with age. NPH is caused by abnormal cerebrospinal fluid (CSF) reabsorption and manifested as a balance impairment, urinary incontinence and dementia development. These symptoms are potentially reversible if recognized early. Diagnosis of NPH is difficult and can be easily mistaken for other neurodegenerative disorders, which makes NPH one of the major misdiagnosed diseases worldwide. The aim of the study was to find out the appropriate combination of indicators, based on CSF steroids, which would contribute to a clearer NPH diagnosis. The levels of CSF cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, 16α-OH-DHEA and aldosterone (all LC-MS/MS) were determined in our patients (n=30; NPH, 65–80 years) and controls (n=10; 65–80 years). The model of orthogonal projections to latent structures (OPLS) was constructed to predict NPH. Cortisone, 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, aldosterone, 7α-OH-DHEA /DHEA, 7-oxo-DHEA/7α-OH-DHEA, 7β-OH-DHEA/7-oxo-DHEA and 16α-OH-DHEA/DHEA in the CSF were identified as the key predictors and the model discriminated patients from controls with 100% sensitivity and 100% specificity. The suggested model would contribute to early and accurate NPH diagnosis, enabling promptly treatment of the disease.

Multidetector Computed Tomography and Magnetic Resonance Imaging Evaluation of Craniovertebral junction Abnormalities.

Background:Craniovertebral junction (CVJ) abnormalities constitute an important group of treatable neurological disorders with diagnostic dilemma. Their precise diagnosis, identification of probable etiology, and pretreatment evaluation significantly affects prognosis and quality of life of patients.Aims:The study was to classify various craniovertebral junction disorders according to their etiology and to define the importance of precise diagnosis for pretreatment evaluation with multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI).Materials and Methods:This is a prospective observational study of 62 patients referred to our department between October 2012 and September 2014. All patients suspected to have a craniovertebral junction disorder were included in the study, from all age groups and both genders. Detailed clinical history was taken. Radiographs of cervical spine were collected if available. All patients were subjected to MDCT and/or MRI.Results:In our study of 62 patients; 39 were males and 23 were females, with male to female ratio of 1.6:1. Most common age group was 2nd -3rd decade (19 patients, 30.64%). Developmental anomalies (33 patients, 53.22%) were the most common etiology group followed by traumatic (10 patients, 16.12%), degenerative (eight patients, 12.90%), infective (four patients, 6.45%), inflammatory and neoplastic (three patients each, 4.8%), and no cause found in one patient.Conclusions:CVJ abnormalities constitute an important group of treatable neurological disorders, especially in certain ethnic groups and are approached with much caution by clinicians. Thus, it is essential that radiologists should be able to make a precise diagnosis of craniovertebral junction abnormalities, classify them into etiological group, and rule out important mimickers on MDCT and/or MRI, as this information ultimately helps determine the management of such abnormalities, prognosis, and quality of life of patients.

Sporadic and familial glut1ds Italian patients: A wide clinical variability

PurposeGLUT1 deficiency syndrome is a treatable neurological disorder characterized by developmental delay, movement disorders and epilepsy. It is caused by mutations in the SLC2A1 gene inherited as an autosomal dominant trait with complete penetrance, even if most detected SCL2A1 mutations are de novo. Our aim is to present a wide series of Italian patients to highlight the differences among subjects with de novo mutations and those with familial transmission. MethodsWe present clinical and genetic features in a series of 22 GLUT1DS Italian patients. Our patients were classified in two different groups: familial cases including GLUT1DS patients with genetically confirmed affected relatives and sporadic cases with detection of SLC2A1 de novo mutation. ResultsWe found remarkable differences in the severity of the clinical picture regarding the type of genetic inheritance (sporadic versus familial): sporadic patients were characterized by an earlier epilepsy-onset and higher degree of intellectual disability. No significant differences were found in terms of type of movement disorder, whilst Paroxysmal Exertion-induced Dyskinesia (PED) is confirmed to be the most characteristic movement disorder type in GLUT1DS. In familial cases the clinical manifestation of the disease was particularly variable and heterogeneous, also including asymptomatic patients or those with minimal-symptoms. ConclusionThe finding of a “mild” phenotype in familial GLUT1DS gives rise to several questions: the real incidence of the disease, treatment option with ketogenic diet in adult patients and genetic counseling.

Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: A treatable neurological disorder caused by TPK1 mutations

Thiamine pyrophosphokinase (TPK) produces thiamine pyrophosphate, a cofactor for a number of enzymes, including pyruvate dehydrogenase and 2-ketoglutarate dehydrogenase. Episodic encephalopathy type thiamine metabolism dysfunction (OMIM 614458) due to TPK1 mutations is a recently described rare disorder. The mechanism of the disease, its phenotype and treatment are not entirely clear.We present two patients with novel homozygous TPK1 mutations (Patient 1 with p.Ser160Leu and Patient 2 with p.Asp222His). Unlike the previously described phenotype, Patient 2 presented with a Leigh syndrome like non-episodic early-onset global developmental delay, thus extending the phenotypic spectrum of the disorder. We, therefore, propose that TPK deficiency may be a better name for the condition. The two cases help to further refine the neuroradiological features of TPK deficiency and show that MRI changes can be either fleeting or progressive and can affect either white or gray matter. We also show that in some cases lactic acidosis can be absent and 2-ketoglutaric aciduria may be the only biochemical marker. Furthermore, we have established the assays for TPK enzyme activity measurement and thiamine pyrophosphate quantification in frozen muscle and blood. These tests will help to diagnose or confirm the diagnosis of TPK deficiency in a clinical setting.Early thiamine supplementation prevented encephalopathic episodes and improved developmental progression of Patient 1, emphasizing the importance of early diagnosis and treatment of TPK deficiency. We present evidence suggesting that thiamine supplementation may rescue TPK enzyme activity.Lastly, in silico protein structural analysis shows that the p.Ser160Leu mutation is predicted to interfere with TPK dimerization, which may be a novel mechanism for the disease.

Diagnosis and management of myasthenia gravis

AbstractMyasthenia gravis is the most common primary disorder of neuromuscular transmission and one of the most treatable neurological disorders. In this review, Dr Sathasivam examines the epidemiology, presentation, aetiology, diagnosis and treatment of myasthenia gravis. Copyright © 2014 John Wiley &amp; Sons

Diagnostic value of cerebrospinal fluid markers

Differential diagnosis of Creutzfeldt–Jakob disease (CJD) versus other—sometimes treatable—neurological disorders is challenging, owing in part to uncertainty about the utility of recommended diagnostic tools. Two recent studies have addressed the reliability of cerebrospinal fluid biomarkers in identification of patients with sporadic CJD among clinically suspected cases.