Nicholas E. Johnson

Anti-NMDA receptor encephalitis causing prolonged nonconvulsive status epilepticus

Anti-NMDA receptor encephalitis is characterized by dyskinesias, psychosis, and seizures1 secondary to antibodies to the NR1-NR2B heteromer of the NMDA receptor.2 This syndrome, more common in women, is often related to an ovarian tumor1; the prognosis is better if the tumor is identified within 3 months of onset. Our case had nonconvulsive status epilepticus lasting 6 months, with marked improvement following removal of the ovarian tumor. ### Case report. A 35-year-old woman, previously healthy and without history of psychosis, had a 3-week history of progressive headaches, short-term memory loss, and irritability. On admission, she was psychotic, requiring physical and chemical restraints. She was unable to follow commands, had echolalia, and had occasional dystonic posturing of her limbs. One week later, she became unresponsive to external stimuli. An EEG demonstrated persistent nonconvulsive status epilepticus (NCSE). Initial CSF studies were remarkable for a lymphocytic pleocytosis with 386 leukocytes. Brain MRI showed diffusion-weighted imaging hyperintensity in the right medial temporal lobe transitioning to fluid-attenuated inversion recovery hyperintensity on repeat imaging (figure 1A). Tests for multiple viral and bacterial pathogens, including herpes simplex virus, were negative. A paraneoplastic …

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1)

Objective: To determine the most critical symptoms in a national myotonic dystrophy type 1 (DM1) population and to identify the modifying factors that have the greatest effect on the severity of these symptoms. Methods: We performed a cross-sectional study of 278 adult patients with DM1 from the national registry of patients with DM1 between April and August 2010. We assessed the prevalence and relative significance of 221 critical DM1 symptoms and 14 disease themes. These symptoms and themes were chosen for evaluation based on prior interviews with patients with DM1. Responses were categorized by age, CTG repeat length, gender, and duration of symptoms. Results: Participants with DM1 provided symptom rating survey responses to address the relative frequency and importance of each DM1 symptom. The symptomatic themes with the highest prevalence in DM1 were problems with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%). Participants identified fatigue and limitations in mobility as the symptomatic themes that have the greatest effect on their lives. We found an association between age and the average prevalence of all themes (p < 0.01) and between CTG repeat length and the average effect of all symptomatic themes on participant lives (p < 0.01). Conclusions: There are a wide range of symptoms that significantly affect the lives of patients with DM1. These symptoms, some previously underrecognized, have varying levels of importance in the DM1 population and are nonlinearly dependent on patient age and CTG repeat length.

Myotonic dystrophy: From bench to bedside

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant disorders classically characterized by muscle weakness, myotonia, and early-onset cataracts. Patients may also experience dysfunction of the heart, brain, gastrointestinal, endocrine, skin, and respiratory systems. The pathogenesis of myotonic dystrophy is related to trinucleotide (DM1) and tetranucleotide (DM2) repeat expansions that produce toxic mutant mRNA with subsequent interference of RNA-splicing mechanisms. Optimal disease management includes symptomatic care, screens for asymptomatic disease, counseling, and a multidisciplinary approach. The authors review the pathogenesis, clinical features, diagnostic tests, and standard management of DM1 and DM2 and outline promising clinical research for patients with these disorders.

Myotonic Dystrophy Health Index: initial evaluation of a disease-specific outcome measure.

Introduction: In preparation for clinical trials we examine the validity, reliability, and patient understanding of the Myotonic Dystrophy Health Index (MDHI). Methods: Initially we partnered with 278 myotonic dystrophy type‐1 (DM1) patients and identified the most relevant questions for the MDHI. Next, we used factor analysis, patient interviews, and test–retest reliability assessments to refine and evaluate the instrument. Lastly, we determined the capability of the MDHI to differentiate between known groups of DM1 participants. Results: Questions in the final MDHI represent 17 areas of DM1 health. The internal consistency was acceptable in all subscales. The MDHI had a high test–retest reliability (ICC = 0.95) and differentiated between DM1 patient groups with different disease severities. Conclusions: Initial evaluation of the MDHI provides evidence that it is valid and reliable as an outcome measure for assessing patient‐reported health. These results suggest that important aspects of DM1 health may be measured effectively using the MDHI. Muscle Nerve 49: 906–914, 2014

Plasma exchange versus intravenous immunoglobulin for myasthenia gravis crisis: An acute hospital cost comparison study

Objective: To compare the short-term financial costs of treating a patient in myasthenia gravis crisis with intravenous immunoglobulin (IVIG) versus plasma exchange. Methods: An itemized comparative cost-minimization analysis of IVIG versus plasma exchange for myasthenia gravis crisis was performed. Calculations were based on each therapys implementation cost, associated hospitalization times, and predicted cost to treat known complications. A cost superiority determination was proposed based on the total cost profile of each therapy. Results: The difference in total cost favored IVIG over plasma exchange with an average savings of

Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease

22,326 per patient. Sensitivity analysis demonstrated that overall costs are highly dependent on IVIG dosing, hospital lengths of stay, and the number of plasma exchange days required. Conclusions: The use of IVIG for myasthenia gravis crisis may be a short-term cost minimizing therapy compared with plasma exchange. Additional prospective studies are required to evaluate the extended cost profile and efficacy of these therapies.

Quality-of-life in Charcot–Marie–Tooth disease: The patient’s perspective

IMPORTANCE Disease severity of childhood Charcot-Marie-Tooth disease (CMT) has not been extensively characterized, either within or between types of CMT to date. OBJECTIVE To assess the variability of disease severity in a large cohort of children and adolescents with CMT. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study was conducted among 520 children and adolescents aged 3 to 20 years at 8 universities and hospitals involved in the Inherited Neuropathies Consortium between August 6, 2009, and July 31, 2014, in Australia, Italy, the United Kingdom, and the United States. Data analysis was conducted from August 1, 2014, to December 1, 2015. MAIN OUTCOMES AND MEASURES Scores on the Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS), a well-validated unidimensional clinical outcome measure to assess disease severity. This instrument includes 11 items assessing fine and gross motor function, sensation, and balance to produce a total score ranging from 0 (unaffected) to 44 (severely affected). RESULTS Among the 520 participants (274 males) aged 3 to 20 years, CMT type 1A (CMT1A) was the most prevalent type (252 [48.5%]), followed by CMT2A (31 [6.0%]), CMT1B (15 [2.9%]), CMT4C (13 [2.5%]), and CMTX1 (10 [1.9%]). Disease severity ranged from 1 to 44 points on the CMTPedS (mean [SD], 21.5 [8.9]), with ankle dorsiflexion strength and functional hand dexterity test being most affected. Participants with CMT1B (mean [SD] CMTPedS score, 24.0 [7.4]), CMT2A (29.7 [7.1]), and CMT4C (29.8 [8.6]) were more severely affected than those with CMT1A (18.9 [7.7]) and CMTX1 (males: 15.3 [7.7]; females: 13.0 [3.6]) (P < .05). Scores on the CMTPedS tended to worsen principally during childhood (ages, 3-10 years) for participants with CMT4C and CMTX1 and predominantly during adolescence for those with CMT1B and CMT2A (ages, 11-20 years), while CMT1A worsened consistently throughout childhood and adolescence. For individual items, participants with CMT4C recorded more affected functional dexterity test scores than did those with all other types of CMT (P < .05). Participants with CMT1A and CMTX1 performed significantly better on the 9-hole peg test and balance test than did those with all other types of CMT (P < .05). Participants with CMT2A had the weakest grip strength (P < .05), while those with CMT2A and CMT4C exhibited the weakest ankle plantarflexion and dorsiflexion strength, as well as the lowest long jump and 6-minute walk test distances (P < .05). Multiple regression modeling identified increasing age (r = 0.356, β = 0.617, P < .001) height (r = 0.251, β = 0.309, P = .002), self-reported foot pain (r = 0.162, β = .114, P = .009), and self-reported hand weakness (r = 0.243, β = 0.203, P < .001) as independent predictors of disease severity. CONCLUSIONS AND RELEVANCE These results highlight the phenotypic variability within CMT genotypes and mutation-specific manifestations between types. This study has identified distinct functional limitations and self-reported impairments to target in future therapeutic trials.

Education Research: Neurology training reassessed The 2011 American Academy of Neurology Resident Survey results

This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance of each symptom identified. Prevalence and symptom impact were analyzed by age, symptom duration, gender, Charcot-Marie-Tooth type, and employment status. 407 participants returned the survey, identifying foot and ankle weakness (99.7%) and impaired balance (98.6%) as the most prevalent themes. Foot and ankle weakness and limitations with mobility were the themes with the highest impact. Both symptom prevalence and impact gradually increased with age and symptom duration. Several themes were more prevalent in women with Charcot-Marie-Tooth, including activity limitations, pain, fatigue, hip-thigh weakness, and gastrointestinal issues. All of the themes, except emotional or body image issues, were more prevalent among unemployed individuals. There were minimal differences in symptom prevalence between Charcot-Marie-Tooth types. There are multiple symptoms that impact Charcot-Marie-Tooth quality-of-life in adults. These symptoms have different levels of importance, are readily recognized by patients, and represent critical areas of Charcot-Marie-Tooth health.

Consensus on cerebral involvement in myotonic dystrophy: Workshop report: May 24–27, 2013, Ferrere (AT), Italy

Objective: To assess the strengths and weaknesses of neurology resident education using survey methodology. Methods: A 27-question survey was sent to all neurology residents completing residency training in the United States in 2011. Results: Of eligible respondents, 49.8% of residents returned the survey. Most residents believed previously instituted duty hour restrictions had a positive impact on resident quality of life without impacting patient care. Most residents rated their faculty and clinical didactics favorably. However, many residents reported suboptimal preparation in basic neuroscience and practice management issues. Most residents (71%) noted that the Residency In-service Training Examination (RITE) assisted in self-study. A minority of residents (14%) reported that the RITE scores were used for reasons other than self-study. The vast majority (86%) of residents will enter fellowship training following residency and were satisfied with the fellowship offers they received. Conclusions: Graduating residents had largely favorable neurology training experiences. Several common deficiencies include education in basic neuroscience and clinical practice management. Importantly, prior changes to duty hours did not negatively affect the resident perception of neurology residency training.

Patient Identified Disease Burden in Facioscapulohumeral Muscular Dystrophy

Thirty-four clinicians, scientists and representatives from industries convened for a workshop on cerebral involvement in myotonic dystrophy (DM). The workshop was held in Ferrere (Asti) from May 24th to 27th 2013 and as the previous one [1] had the purpose to stimulate the research on CNS dysfunction in DM and to discuss major issues regarding CNS involvement. Classically viewed as a neuromuscular disease, for many years research on DM has been principally focused on muscular aspects. Therefore few data are available for CNS involvement. With new therapeutic developments with potential to affect pathophysiology across multiple tissues and organ systems it will be mandatory to increase our understanding of CNS pathophysiology in order to appropriately monitor whether or not there is beneficial effect in CNS. Indeed CNS dysfunction is one of the major issue affecting quality of life in DM patients thus it has to be appropriately considered in planning clinical trials. This workshop included different themes covering all the topics of DM CNS involvement. CNS research needs to proceed faster and consensus has to be established in the major themes of CNS study. The present report describes the major issues that emerged during the workshop, with the aim of updating and stimulating research in this critical field.