Jonathan Howard

Testing tic suppression: comparing the effects of dexmethylphenidate to no medication in children and adolescents with attention-deficit/hyperactivity disorder and Tourette's disorder

OBJECTIVE The aim of this study was to conduct a pilot study testing whether single-dose, immediate-release dexmethylphenidate (dMPH) can facilitate tic suppression in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and Tourettes disorder (TD) or chronic tic disorders. The primary hypothesis is that dMPH will improve behaviorally reinforced tic suppression in a standard tic suppression paradigm (TSP). METHODS Ten children with ADHD and TD were given dMPH on one visit and no medication on another, using a random crossover design. On both days, following a baseline period, subjects were reinforced for suppressing tics using a standard TSP. RESULTS Thirteen subjects were enrolled; 10 subjects (mean age 12.7 +/- 2.6; 90% male) completed all study procedures. Relative to the no-medication condition, tics were reduced when children were given a single dose of dMPH. Behavioral reinforcement of tic suppression resulted in lower rates of tics compared to baseline, but dMPH did not enhance this suppression. CONCLUSION Preliminary results indicate replication of prior studies of behavioral tic suppression in youths with TD and without ADHD. In addition, our findings indicate tic reduction (and not tic exacerbation) with acute dMPH challenge in children and adolescents with ADHD and TD.

Association of Deep Gray Matter Damage With Cortical and Spinal Cord Degeneration in Primary Progressive Multiple Sclerosis

IMPORTANCE The investigation of cortical gray matter (GM), deep GM nuclei, and spinal cord damage in patients with primary progressive multiple sclerosis (PP-MS) provides insights into the neurodegenerative process responsible for clinical progression of MS. OBJECTIVE To investigate the association of magnetic resonance imaging measures of cortical, deep GM, and spinal cord damage and their effect on clinical disability. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of 26 patients with PP-MS (mean age, 50.9 years; range, 31-65 years; including 14 women) and 20 healthy control participants (mean age, 51.1 years; range, 34-63 years; including 11 women) enrolled at a single US institution. Clinical disability was measured with the Expanded Disability Status Scale, 9-Hole Peg Test, and 25-Foot Walking Test. We collected data from January 1, 2012, through December 31, 2013. Data analysis was performed from January 21 to April 10, 2015. MAIN OUTCOMES AND MEASURES Cortical lesion burden, brain and deep GM volumes, spinal cord area and volume, and scores on the Expanded Disability Status Scale (score range, 0 to 10; higher scores indicate greater disability), 9-Hole Peg Test (measured in seconds; longer performance time indicates greater disability), and 25-Foot Walking Test (test covers 7.5 m; measured in seconds; longer performance time indicates greater disability). RESULTS The 26 patients with PP-MS showed significantly smaller mean (SD) brain and spinal cord volumes than the 20 control group patients (normalized brain volume, 1377.81 [65.48] vs 1434.06 [53.67] cm3 [P = .003]; normalized white matter volume, 650.61 [46.38] vs 676.75 [37.02] cm3 [P = .045]; normalized gray matter volume, 727.20 [40.74] vs 757.31 [38.95] cm3 [P = .02]; normalized neocortical volume, 567.88 [85.55] vs 645.00 [42.84] cm3 [P = .001]; normalized spinal cord volume for C2-C5, 72.71 [7.89] vs 82.70 [7.83] mm3 [P < .001]; and normalized spinal cord volume for C2-C3, 64.86 [7.78] vs 72.26 [7.79] mm3 [P =.002]). The amount of damage in deep GM structures, especially with respect to the thalamus, was correlated with the number and volume of cortical lesions (mean [SD] thalamus volume, 8.89 [1.10] cm3; cortical lesion number, 12.6 [11.7]; cortical lesion volume, 0.65 [0.58] cm3; r = -0.52; P < .01). Thalamic atrophy also showed an association with cortical lesion count in the frontal cortex (mean [SD] thalamus volume, 8.89 [1.1] cm3; cortical lesion count in the frontal lobe, 5.0 [5.7]; r = -0.60; P < .01). No association was identified between magnetic resonance imaging measures of the brain and spinal cord damage. CONCLUSIONS AND RELEVANCE In this study, the neurodegenerative process occurring in PP-MS appeared to spread across connected structures in the brain while proceeding independently in the spinal cord. These results support the relevance of anatomical connectivity for the propagation of MS damage in the PP phenotype.

Phase-Sensitive Inversion-Recovery MRI Improves Longitudinal Cortical Lesion Detection in Progressive MS

Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross-sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leucocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up.

Hypogeusia as a symptom of neuromyelitis optica spectrum disorder.

There are multiple etiologies of hypogeusia listed in the literature including, but not limited to, certain medications, brainstem and thalamic lesions, tumors, mononeuropathy (Bells’ palsy), and demyelinating disorders.1 To the best of our knowledge, there are numerous case reports of hypogeusia/ageusia as a symptom of multiple sclerosis (MS),2,3,4 however there are no previous reports of hypogeusia as a symptom of neuromyelitis optica (NMO). We describe a 27 year old African-American female who presented complaining of diminished sensation of taste on the left side, diplopia and nausea. Her exam was notable for decreased taste to all modalities in both anterior and posterior left side of the tongue and horizontal nystagmus on leftward gaze. Her motor, sensory and cerebellar functions were otherwise intact, with normal reflexes. We performed a thorough literature search, and found previous similar presentations in patients with MS, however none have been reported with NMO. Plaque locations discussed in previous case reports which were associated with hypogeusia/ageusia were thalamus, lateral midpontine tegmentum and posterior medulla. The patient’s workup included serology and cerebrospinal fluid (CSF) testing, as well as brain magnetic resonance imaging (MRI). The patient’s basic labs, including complete blood count (CBC), basic metabolic panel, liver function panel, anti-nuclear antibody (ANA), erythrocyte sedimentation rate (ESR) were all negative or normal, except for presence of aquaporin 4 antibody. Her CSF studies were unremarkable. Her brain MRI was significant for T2/FLAIR hyperintensity in left midpontine tegmentum (Figure 1). There were no lesions identified on MRI of the cervical spine. Based on these tests she was diagnosed with an NMO spectrum disorder (NMOSD).

Acute exacerbation of multiple sclerosis presenting with facial metamorphopsia and palinopsia.

We discuss the case of a patient with a known history of relapsing–remitting multiple sclerosis (MS) who presented with the isolated complaint of altered visual perception in the absence of abnormalities on ophthalmological examination. To the best of the authors’ knowledge, this is the first documented case of both facial metamorphopsia and palinopsia occurring as the symptoms of demyelinating brain lesions consistent with an acute MS exacerbation. These symptoms appear to be related to active demyelination that either involved the optic radiations in the visual pathway or the visual association area in the temporo-occipital region of the left hemisphere.

Drug-induced leukoencephalopathy presenting as catatonia

We discuss the case of a 35-year-old woman who presented with thought impoverishment, disorganized behavior, and echolalia. The patients condition progressed to treatment-refractory catatonia. She was started on oral Coenzyme Q10 after magnetic resonance imaging of the brain showed findings consistent with drug-induced leukoencephalopathy (DIL). Following improvement, she acknowledged cocaine use that suggested a diagnosis of cocaine-induced leukoencephalopathy (CIL). This case report seeks to elucidate radiological and clinical features of DIL.

An MRI evaluation of grey matter damage in African Americans with MS

OBJECTIVE Multiple sclerosis (MS) is less prevalent in African Americans (AAs) than Caucasians (CAs) but in the former the disease course tends to be more severe. In order to clarify the MRI correlates of disease severity in AAs, we performed a multimodal brain MRI study to comprehensively assess the extent of grey matter (GM) damage and the degree of functional adaptation to structural damage in AAs with MS. METHODS In this cross-sectional study, we characterized GM damage in terms of focal lesions and volume loss and functional adaptation during the execution of a simple motor task on a sample of 20 AAs and 20 CAs with MS and 20 healthy controls (CTRLs). RESULTS In AAs, we observed a wider range of EDSS scores than CAs, with multisystem involvement being more likely in AAs (p < 0.01). While no significant differences were detected in lesion loads and global brain volumes, AAs showed regional atrophy in the posterior lobules of cerebellum, temporo-occipital and frontal regions in comparison with CAs (p < 0.01), with cerebellar atrophy being the best metric in differentiating AAs from CAs (p = 0.007, AUC = 0.96 and p = 0.005, AUC = 0.96, respectively for right and left cerebellar clusters). In AAs, the functional analysis of cortical activations showed an increase in task-related activation of areas involved in high level processing and a decreased activation in the medial prefrontal cortex compared to CAs. INTERPRETATION In our study, the direct comparison of AAs and CAs points to cerebellar atrophy as the main difference between subgroups.

Concurrent LETM and nerve root enhancement in spinal neurosarcoid: A case series

Spinal neurosarcoidosis is a rare form of neurosarcoid which can be challenging to diagnose given its clinical or radiographic findings are often indistinguishable from other causes of spinal demyelinating disease. We present a series of three patients with spinal neurosarcoid, all of whom demonstrated concurrent longitudinally enhancing transverse myelitis as well as spinal nerve root enhancement. These findings may be suggestive of spinal neurosarcoid and may help clinicians make the diagnosis as well as reduce the need for invasive biopsy.

An educational initiative to improve medical student awareness about brain death

OBJECTIVE Medical student knowledge about brain death determination is limited. We describe an educational initiative to improve medical student awareness about brain death and assess the impact of this initiative. SUBJECTS AND METHODS Beginning in July 2016, students at our medical school were required to attend a 90-min brain death didactic and simulation session during their neurology clerkship. Students completed a test immediately before and after participating in the initiative. RESULTS Of the 145 students who participated in this educational initiative between July 2016 and June 2017, 124 (86%) consented to have their data used for research purposes as part of a medical education registry. Students correctly answered a median of 53% of questions (IQR 47-58%) on the pretest and 86% of questions (IQR 78-89%) on the posttest (p < .001). Comfort with both performing a brain death evaluation and talking to a family about brain death improved significantly after this initiative (18% of students were comfortable performing a brain death evaluation before the initiative and 86% were comfortable doing so after the initiative, p < .001; 18% were comfortable talking to a family about brain death before the initiative and 76% were comfortable doing so after the initiative, p < .001). CONCLUSIONS Incorporation of simulation in undergraduate medical education is high-yield. At our medical school, knowledge about brain death and comfort performing a brain death exam or talking to a family about brain death was limited prior to development of this initiative, but awareness and comfort dealing with brain death improved significantly after this initiative.

Disseminated HSV-2 presenting with relapsing encephalomyelitis

A previously healthy 39-year-old woman presented with 3 weeks of progressive leg numbness. Examination showed mild bilateral iliopsoas weakness and patchy leg numbness. She was admitted, and spinal MRI revealed T2 enhancing thoracic lesions, nonenhancing cervical cord lesions (figure, A), and subtle pial and cauda equina enhancement (figure, B). Brain MRI revealed multiple periventricular T2 hyperintensities (figure, C). Since the diagnosis of multiple sclerosis (MS) was considered likely, lumbar puncture (LP) was deferred and she received 5 days of IV methylprednisolone. One week later, she developed increasing right-sided hearing loss and vertigo with right cochlear enhancement (figure, D). Two weeks later, a morbilliform and vesicular flank and trunk rash appeared (figure, E and F). She was readmitted and treated with IV acyclovir for presumed disseminated varicella zoster virus (VZV). LP revealed a lymphocytic pleocytosis (90 leukocytes, 100% lymphocytes) and elevated protein (150 mg/dL). Oligoclonal bands were positive, and neuromyelitis optica and human T-cell lymphotropic virus–1 antibodies were negative. A PCR encephalitis panel was positive for herpes simplex virus (HSV)–2 and negative for VZV and HSV-1. Skin biopsy viral culture and PCR were positive for HSV. Three weeks after rash onset, the patient developed worsening leg numbness, received 5 more days of IV methylprednisolone, and soon after developed severe ataxia and weakness. Repeat MRI revealed new pontine lesions atypical for MS, punctate lesions following a vascular distribution, and new enhancing spinal cord lesions (figure, G and H). Repeat LP revealed a decreasing leukocyte count (17 leukocytes) and rising protein (298 mg/dL). CSF HSV-2 PCR was now negative, yet quantitative ELISA revealed positive HSV-2 immunoglobulin G (IgG) (8.83 antibody index [AI]) and negative HSV-1 IgG (0.3 [reference range 0.9 AI]). CSF HSV-1 and HSV-2 immunoglobulin M (IgM) (1.15) and IgG titers were elevated (27.93 [reference range 0.9 AI]). A unifying diagnosis of HSV-2 encephalomyelitis was made. The patient was treated with plasmapheresis, followed by IV immunoglobulin (IVIG), concurrently with 6 weeks of IV acyclovir. A follow-up LP 3 weeks after treatment initiation demonstrated decreasing HSV IgM (0.22 AI) and IgG (7.96 AI) titers, pleocytosis (6 leukocytes), and protein (111 mg/dL), consistent with declining inflammation. Monthly follow-up imaging showed interval resolution of spinal enhancement and no new lesions, commensurate with resolving sensory symptoms and ataxia.