Contactin-Associated Protein-Like 2-Related Peripheral Nerve Hyperexcitability Associated With Charcot-Marie-Tooth Type 4F.

Contactin-associated protein-like 2 autoimmunity is an uncommon disorder resulting in peripheral nerve hyperexcitability or encephalitis. In a fifth of cases, onset may be provoked by thymoma, but other associations are largely unknown. We report a patient with anti-contactin-associated protein-like 2-related peripheral nerve hyperexcitability arising in the setting of Charcot-Marie-Tooth type 4F and discuss potential mechanisms underlying the association.

Diagnosis of orthostatic tremor using smartphone accelerometry.

BACKGROUND: Primary orthostatic tremor (OT) is a rare movement disorder characterized by a 13-18 Hz leg tremor, which arises when standing and is relieved by walking/sitting. Those affected generally do not fall, but experience fear of falling, lessened by ambulation. Because of its low amplitude, the tremor is not readily visible, and diagnosis requires confirmation with surface electromyography (sEMG). Recently, applications using the accelerometer feature of smartphones have been used to detect and quantify tremors, including OT, though the accuracy of smartphone accelerometry (SPA) in diagnosing OT is unknown. METHODS: We completed SPA in consecutive adults (18+ years), who presented to our neurology clinic with either subjective leg shakiness upon standing or unsteadiness when standing that lessened with ambulation, which comprised 59 of 2578 patients. We assessed tremor using the StudyMyTremor application on an iPhone 6 s adhered with tape to the patient's tibialis anterior. Surface electromyography was completed on the same muscle. The primary outcome of this study was to determine SPA's sensitivity and specificity in detecting OT compared with surface electromyography. RESULTS: Fifty-nine patients with the following diagnoses were included: OT (6), Parkinson's disease, Hereditary Spastic Paraplegia, orthostatic hypotension, essential tremor, spinal cerebellar ataxia, sensory ataxia and functional movement disorder. Smartphone accelerometry detected a 13-18 Hz tremor in 5 of 6 patients diagnosed with OT by sEMG with no false positives in other conditions, yielding a sensitivity of 83%, specificity of 100% in the cohort we studied. CONCLUSIONS: Though a larger sample size is desirable, preliminary data suggest that smartphone accelerometry is an alternative to surface electromyography in diagnosing OT.

Multi-Residency Implementation of an Online Movement Disorders Curriculum Based on Real Patient Videos.

Background: In-person didactic education in residency has numerous challenges including inconsistent availability of faculty and residents, limited engagement potential, and non-congruity with clinical exposure. Methods: An online curriculum in movement disorders was implemented across nine neurology residency programs (six intervention, three control), with the objective to determine feasibility, acceptability, and knowledge growth from the curriculum. Residents in the intervention group completed ten modules and a survey. All groups completed pre-, immediate post-, and delayed post-tests. Results: Eighty-six of 138 eligible housestaff (62.3%) in the intervention group completed some modules and 74 completed at least half of modules. Seventy-four, 49, and 30 residents completed the pre-, immediate post-, and delayed post-tests respectively. Twenty-five of 42 eligible control residents (59.5%) completed at least one test. Mean pre-test scores were not significantly different between groups (6.33 vs. 6.92, p = 0.18); the intervention group had significantly higher scores on immediate post- (8.00 vs. 6.79, p = 0.001) and delayed post-tests (7.92 vs. 6.92, p = 0.01). Residents liked having a framework for movement disorders, appreciated the interactivity, and wanted more modules. Residents completed the curriculum over variable periods of time (1-174 days), and at different times of day. Discussion: This curriculum was feasible to implement across multiple residency programs. Intervention group residents showed sustained knowledge benefit after participating, and residents took advantage of its flexibility in their patterns of module completion. Similar curricula may help to standardize certain types of clinical learning and exposure across residency programs. Highlights: Interactive online tools for resident didactic learning are valuable to residents. Residents learn from interactive online curricula, find the format engaging, and take advantage of the flexibility of online educational tools. Beginner learners appreciate algorithms that help them to approach a new topic.

Comparing No-Show Rates of Neurology Outpatients with and without Parkinson's Disease: A Real-World Assessment of the Parkinsonian Personality Profile.

BACKGROUND: Parkinson's disease (PD) has been hypothesized to be associated with certain personality traits, including conscientiousness and punctuality. However, research aimed at quantifying these traits is largely derived from questionnaire-based personality inventories rather than real-world observations. OBJECTIVE: To explore the presence of a parkinsonian personality profile by assessing the no-show rate of patients with PD versus other neurological disorders. METHODS: We extracted data from our electronic health record for all neurology appointments over a 78-month interval. Additionally, we obtained primary care appointment data for the same patients over the same timeframe. For each appointment we collected appointment date/time, check-in time, provider, age, sex, insurance type, days between appointment date and scheduling, diagnosis code, and no-show status. RESULTS: 19,433 unique patients (400 with PD) accounting for a total of 252,347 outpatient appointments were included in our analysis. The overall no-show rate for PD patients was 3% versus 7.4% for patients with other neurologic disorders (OND). No show rates for PD patients were lower than those with OND for both neurology appointments (2.7% versus 13.6%) and for primary care visits (3.1% versus 5.9%). CONCLUSIONS: Patients with PD have lower no-show rates than patients with OND. Additionally, the no-show rate for patients with PD did not differ between their neurology and primary care appointments, confirming that patient's personality rather than provider traits account for this difference, and supporting the presence of a parkinsonian personality.

Apomorphine injections: predictors of initial common adverse events and long term tolerability.

BACKGROUND: Apomorphine injections effectively abort "off" episodes in Parkinson's disease (PD). However, their use is limited by actual and perceived adverse events (AE). To our knowledge, no study has evaluated for predictors of these problems. OBJECTIVES: To assess predictors of initial common AE and long-term tolerability of apomorphine injections in PD. METHODS: We prospectively monitored for AE in 28 consecutive PD patients receiving initial apomorphine injections. Sequential visual analogue scale scores for nausea and in standing systolic blood pressure drops at baseline (mean of 2 assessments), 10, 20, and 40 min post-injection were acquired. Assessed historic variables included patient demographics and clinical data, treatment histories, previous AE to other dopaminergic treatments and whether patients received the recommended three day pre-treatment dose of trimethobenzamide. We also correlated the L-dopa equivalent doses with apomorphine dose needed to turn "on". RESULTS: No patient demographic or previous history of dopaminergic AE predicted nausea, except for baseline pre-injection nausea that day at baseline. Three days of trimethobenzamide, as recommended, was actually associated with more nausea than a single dose or no dose, even though a lack of association after matched analysis was found. A younger patient age was associated with hypotension. L-dopa equivalent dose modestly correlated with final apomorphine dose to turn "on". CONCLUSION: A previous history of nausea and hypotension, and older age should not dissuade a trial of apomorphine if clinically justified. A three day pre-treatment dose of trimethobenzamide, as recommended in the United States, does not reduce nausea.

Periodic eyelid opening associated with burst-suppression electroencephalography due to hypoxic ischemic injury.

BACKGROUND: We report four patients who developed periodic eyelid opening following hypoxic ischemic injury. This manuscript reviews the clinical course of our patients as well as previously published cases and discusses the neuroanatomical basis of eyelid opening. METHODS: Data were collected from the patients' electronic medical record and digital electroencephalography recordings. RESULTS: In all patients, periodic eyelid opening was associated with a burst-suppression pattern on electroencephalography (EEG). Rapid eyelid opening appeared with the onset of bursts, while slow eyelid closure coincided with periods of suppression. Progressive rostrocaudal deterioration in brainstem function ensued, in each case culminating in brain death. CONCLUSIONS: Our experience and prior reports suggest that periodic eyelid opening following cardiac arrest is associated with a burst-suppression pattern on EEG. Since burst-suppression is highly (though not invariably) predictive of a poor outcome in this patient population, intensivists should be familiar with this neurological sign. Prospective studies are needed to define the neurophysiology of this phenomena and clarify its clinical significance.

Effect of tetrabenazine on motor function in patients with huntington disease.

INTRODUCTION: Tetrabenazine (TBZ) reduces chorea related to Huntington disease (HD); however, it is uncertain whether this effect improves functionally relevant motor skills such as hand coordination and balance. The objective of this study was to provide pilot data regarding three motor function tests, which might be useful in monitoring symptom progression and therapeutic response, pending formal validation. METHODS: The authors assessed 11 ambulatory patients with HD-related chorea on two occasions: (1) while off TBZ (either prior to starting therapy or following a >24 h washout) and (2) when on a stable dose of TBZ, titrated to optimal effect. Study evaluations included the Jebsen-Taylor Hand Function Test (JTHFT) and Berg Balance Scale, a timed 25-foot walk, the Montreal Cognitive Assessment (MoCA) and the complete United Huntington Disease Rating Scale (UHDRS). RESULTS: Maximal chorea scores (UHDRS item 12) improved from 11.1 ± 2.9 to 8.5 ± 3.9 while on TBZ (P = 0.03), but we could not detect an improvement in functional measures while on TBZ in this small cohort. Scores of the JTHFT were globally slower than published normative data and correlated with MoCA summary scores, but not UHDRS chorea scores. CONCLUSIONS: This pilot study did not detect significant functional gains with chorea suppression. The fact that performance on tests of hand function correlates with MoCA but not UHDRS chorea scores highlights the need for additional treatments targeted toward the cognitive aspects of HD.

Brain-lung-thyroid disease: clinical features of a kindred with a novel thyroid transcription factor 1 mutation.

Brain-lung-thyroid disease is a rare familial disorder caused by mutations in thyroid transcription factor 1, a gene that regulates neuronal migration. We report the clinical features of ten patients from a single family with a novel gene mutation, including observations regarding treatment. Neurologic features of the kindred included developmental delay, learning difficulties, psychosis, chorea, and dystonia. Three patients had a history of seizure, which has not been previously reported in genetically confirmed cases. Low-dose dopamine-receptor blocking drugs were poorly tolerated in 2 patients who received this therapy, levodopa improved chorea in 3 of 4 children, and diazepam was markedly effective in a single adult patient. Chorea related to brain-lung-thyroid disease appears to respond paradoxically to antidopaminergic drugs. The unusual therapeutic response seen in our patients and others may help elucidate how disease-related migratory deficits affect neural pathways associated with motor control.

Efficacy and tolerability of pregabalin in essential tremor: a randomized, double-blind, placebo-controlled, crossover trial.

We performed a double-blind, crossover-design study to assess the tolerability and efficacy of pregabalin (PGB) in patients with essential tremor (ET). Twenty patients (11 women; mean age of 62.2+/-12.7 years, mean ET duration of 25.5+/-14.9 years) with ET were randomized for treatment with PGB (150-600 mg/day) or placebo, titrated over 6 weeks. Identical assessments of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (primary endpoint), Clinical Global Impression of Change (CGI-C), Quality of Life in Essential Tremor Questionnaire (QUEST), Hamilton Anxiety Scale (HAM-A), and a sleep hygiene questionnaire (HD-16) were made at the baseline, at the end of treatment periods for both drug and placebo, and following the 2-week washout period preceding crossover. We found no improvement in any of the TRS measures and a statistically significant worsening of QUEST scores while patients were taking PGB. Adverse events were similar in frequency to previously published studies of PGB, the most common being drowsiness and dizziness.

Impulse-control disorders in Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

Subacute combined degeneration due to copper deficiency.

There is growing clinical evidence supporting a connection between copper deficiency and subacute combined degeneration. While nearly half of patients with copper deficiency myelopathy exhibit MRI abnormalities, signal changes are often ill-defined in distribution. We report a patient with sensory ataxia and spastic paraplegia from copper deficiency whose MRI demonstrates abnormal signal restricted to the dorsal and lateral columns, providing clear radiological support of an association between hypocupremia and combined system degeneration.