Claudio M. de Gusmao

The neurologist's role in supporting transition to adult health care A consensus statement

The child neurologist has a critical role in planning and coordinating the successful transition from the pediatric to adult health care system for youth with neurologic conditions. Leadership in appropriately planning a youths transition and in care coordination among health care, educational, vocational, and community services providers may assist in preventing gaps in care, delayed entry into the adult care system, and/or health crises for their adolescent patients. Youth whose neurologic conditions result in cognitive or physical disability and their families may need additional support during this transition, given the legal and financial considerations that may be required. Eight common principles that define the child neurologists role in a successful transition process have been outlined by a multidisciplinary panel convened by the Child Neurology Foundation are introduced and described. The authors of this consensus statement recognize the current paucity of evidence for successful transition models and outline areas for future consideration.

Dystonia-Causing Mutations as a Contribution to the Etiology of Spasmodic Dysphonia

Objective Spasmodic dysphonia is a focal dystonia of the larynx with heterogeneous manifestations and association with familial risk factors. There are scarce data to allow precise understanding of etiology and pathophysiology. Screening for dystonia-causing genetic mutations has the potential to allow accurate diagnosis, inform about genotype-phenotype correlations, and allow a better understanding of mechanisms of disease. Study Design Cross-sectional study. Setting Tertiary academic medical center. Subjects and Methods We enrolled patients presenting with spasmodic dysphonia to the voice clinic of our academic medical center. Data included demographics, clinical features, family history, and treatments administered. The following genes with disease-causing mutations previously associated with spasmodic dysphonia were screened: TOR1A (DYT1), TUBB4 (DYT4), and THAP1 (DYT6). Results Eighty-six patients were recruited, comprising 77% females and 23% males. A definite family history of neurologic disorder was present in 15% (13 of 86). Average age (± standard deviation) of symptom onset was 42.1 ± 15.7 years. Most (99%; 85 of 86) were treated with botulinum toxin, and 12% (11 of 86) received oral medications. Genetic screening was negative in all patients for the GAG deletion in TOR1A (DYT1) and in the 5 exons currently associated with disease-causing mutations in TUBB4 (DYT4). Two patients tested positive for novel/rare variants in THAP1 (DYT6). Conclusion Genetic screening targeted at currently known disease-causing mutations in TOR1A, THAP1, and TUBB4 appears to have low diagnostic yield in sporadic spasmodic dysphonia. In our cohort, only 2 patients tested positive for novel/rare variants in THAP1. Clinicians should make use of genetic testing judiciously and in cost-effective ways.

Increased Pediatric Functional Neurological Symptom Disorders After the Boston Marathon Bombings: A Case Series

BACKGROUND Functional neurological symptom disorders are frequently the basis for acute neurological consultation. In children, they are often precipitated by high-frequency everyday stressors. The extent to which a severe traumatic experience may also precipitate functional neurological abnormalities is unknown. METHODS For the 2-week period after the Boston Marathon bombings, we prospectively collected data on patients whose presentation suggested a functional neurological symptom disorder. We assessed clinical and demographic variables, duration of symptoms, extent of educational impact, and degree of connection to the Marathon bombing. We contacted all patients at 6 months after presentation to determine the outcome and accuracy of the diagnosis. RESULTS In a parallel study, we reported a baseline of 2.6 functional neurological presentations per week in our emergency room. In the week after the Marathon bombings, this frequency tripled. Ninety-one percent of presentations were delayed by 1 week, with onset around the first school day after a city-wide lockdown. Seventy-three percent had a history of a prior psychiatric diagnosis. At the 6 months follow-up, no functional neurological symptom disorder diagnoses were overturned and no new organic diagnosis was made. CONCLUSIONS Pediatric functional neurological symptom disorder may be precipitated by both casual and high-intensity stressors. The 3.4-fold increase in incidence after the Boston Marathon bombings and city-wide lockdown demonstrates the marked effect that a community-wide tragedy can have on the mental health of children. Care providers must be aware of functional neurological symptom disorders after stressful community events in vulnerable patient populations, particularly those with prior psychiatric diagnoses.

Cerebrospinal fluid shunt-induced chorea: case report and review of the literature on shunt-related movement disorders

Cerebrospinal fluid (CSF) diversion by shunting provides effective management of hydrocephalus.1 However, complication rates of CSF shunts range from 5% to 50%.1–3 Most common are shunt infections and mechanical failures; these may lead either to underdrainage (with re-emergence of hydrocephalus) or overdrainage (with intracranial hypotension and its potential complications, eg, subdural hematoma).3 ,4 Misplacement and migration of shunt catheters may cause seizures, intracerebral haemorrhage, and/or focal neurologic deficits, such as hemiparesis.1 ,2 We report a case of hemichorea after CSF shunt placement, and review the literature on CSF shunt-related movement disorders. A 20-year-old woman with congenital hydrocephalus treated by CSF shunting presented with a purulent discharge from the …

Benign hereditary chorea related to NKX2-1 with ataxia and dystonia

Benign hereditary chorea (BHC) was originally described in 1967, but it was not until 2002 that linkage analysis and positional cloning identified the causative gene, NKX2-1 (also known as TTF-1).1,2 The range of manifestations spans from isolated chorea, pulmonary disease, or thyroid dysfunction, with one-third of patients having the full brain-lung-thyroid syndrome.3 Recent reports have expanded the NKX2-1 phenotype, as patients may present with additional movement disorders such as dystonia and myoclonus.3 We present a case with early-onset chorea, ataxia, and dystonia.

Cerebral vasomotor reactivity monitoring in posterior reversible encephalopathy syndrome

A 25-year-old woman was admitted for vomiting, hypertension and seizures. Magnetic resonance imaging was compatible with posterior reversible encephalopathy syndrome and a transcranial Doppler/vasomotor reactivity study (TCD/VMR) demonstrated loss of vasomotor reactivity. The clinical recovery was concomitant to improvement in the TCD/VMR.

Beyond Dystonia‐Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations

Mutations in the ATP1A3 gene (the α‐3 subunit of the Na+/K+ ATPase) are associated with rapid‐onset dystonia‐parkinsonism; alternating hemiplegia of childhood; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). The authors report 3 cases with pleiotropic movement disorders, including a novel mutation in a patient who presented with ataxia and dysphagia. Case 1 had a history of attention deficit hyperactivity disorder and developed dysphagia, chorea, and limb dystonia after a febrile illness at age 12 years. Case 2 presented with limb dystonia at age 26 years and dysarthia and dysphagia after a febrile illness. Case 3 had a history of learning disability and developed progressive ataxia with cerebellar atrophy at age 20 years. In all cases, deleterious mutations were identified in ATP1A3. They illustrate wide phenotypic variability, including chorea and ataxia. New cases are likely to be diagnosed as knowledge about the phenotypic spectrum expands.

Clinical Reasoning: A 14-year-boy with spells of somnolence and cognitive changes

A 14-year-old boy presented for admission after repeated episodes of lethargy and cognitive changes. He had a history of childhood absence epilepsy that had resolved with antiepileptics discontinued 1 year prior to presentation.

Inherited and Acquired Choreas

Chorea is a symptom of a broad array of genetic, structural, and metabolic disorders. While chorea can result from systemic illness and damage to diverse brain structures, injury to the basal ganglia, especially the putamen or globus pallidus, appears to be a uniting features of these diverse neuropathologies. The timing of onset, rate of progression, and the associated neurological or systemic symptoms can often narrow the differential diagnosis to a few disorders. Recognizing the correct etiology for childhood chorea is critical, as numerous disorders in this category are potentially curable, or are remediable, with early treatment.

“All the soarings of my mind begin in my blood:” central nervous system complication of Waldenström macroglobulinemia

A 76-year-old man was admitted to our hospital for one month of progressive word finding problems. He was diagnosed with Waldenstr€ om macroglobulinemia (WM) two years prior when he presented with fatigue and anemia. The patient carried the MYD88 L265P gene mutation. In the past year, he had developed pancytopenia, elevated serum viscosity, enlarged intra-abdominal lymph nodes, and bilateral pleural effusions. Treatment with monthly infusions of bendamustine and rituximab had been initiated four months before presentation. His absolute lymphocyte count was 1.51 k/uL at the start of therapy, 0.92 k/uL at Cycle 2, 0.75 k/uL at Cycle 3, 1.64 k/uL at Cycle 4, and 1.88 k/uL at four week follow-up after Cycle 4. His counts reached a nadir of 0.24 k/uL midway through the treatment regimen. The patient’s word finding difficulties suggest a lesion in the central nervous system (CNS), specifically in the peri-sylvian region of the left hemisphere, which includes Broca’s area (the center for language expression) anteriorly, Wernicke’s area (the center for language comprehension) posteriorly, and subcortical white matter fibers (arcuate fasciculus) that connect these two regions. The history of WM, and current immunocompromised state due to the disease itself and chemotherapy, raise a broad differential for his neurological symptoms. The most concerning etiologies include arterial or venous occlusion and cerebral infarction due to serum hyperviscosity, cerebral or meningeal inflammation from WM (Bing-Neel syndrome [BNS]), paraneoplastic or other autoimmune encephalitis, or opportunistic infection. On examination, he was alert and interactive with mild bradyphrenia. He had impaired fluency with frequent phonemic and semantic paraphasic errors. He could follow simple commands and repeat short but not longer or more complex sentences. He had right-sided brachiofacial weakness. The remainder of his neurological exam was normal. Abnormal laboratory studies included hemoglobin 11.2 g/dL, white blood cells (WBC) 2.09 k/uL with absolute neutrophil count 0.38 k/uL, absolute lymphocyte count 0.54 k/uL and platelet count 142 3 10/L. Serum protein electrophoresis demonstrated a monoclonal spike in the gamma region of 0.34 g/dL and immunofixation confirmed a monoclonal IgM Kappa paraprotein. Serum IgM level was 379 mg/dL. The patient was in a partial response after 4 cycles of bendamustine and rituximab. The examination supports a mixed aphasia with elements of nonfluency and impaired comprehension that localizes to the left frontal and temporal lobes. The presence of pancytopenia and concurrent immunosuppressive therapy places this patient at elevated risk for progressive multifocal leukoencephalopathy (PML), toxoplasmosis, and primary CNS lymphoma. Furthermore, one should consider CNS abscesses or meningo-encephalitides from fungal (Aspergillus, Cryptococcus), viral (HSV, CMV, VZV) or mycobacterial species. BNS has been described in patients who are responding to therapy for systemic WM [1]. Therefore, the patient’s response to therapy does not exclude the diagnosis of BNS. With a serum IgM level less than 3,000 mg/dL, hyperviscosity is unlikely. The next step in clarifying the diagnosis is a brain MRI with gadolinium. MRI showed multifocal well-demarcated nearly confluent areas of abnormal T2 hyperintensity, predominantly in the subcortical white matter of the left frontal, temporal, parietal, and right frontal lobes (Fig. 1A,B). A dominant lesion in the left anterior frontal sub-cortical white matter was edematous and exerted mass effect on adjacent structures. There was modest reduced diffusivity at the periphery of the left frontal lesion (Fig. 1C). There was no abnormal enhancement of this lesion on post-contrast images. As part of staging for WM, the patient underwent a full body positron emission tomography (PET) scan that showed no systemic 18F-FDG-avid lesions. The left frontal lobe lesion showed reduced 18F-FDG uptake (Fig. 1D). The radiographic findings support a multifocal process with a tumefactive lesion in the left frontal lobe. The juxtacortical white matter hyperintensities on T2-weighted images are consistent with an infiltrative condition. The absence of prominent reduced diffusivity makes primary CNS lymphoma or abscess less likely. Furthermore, the absence of contrast enhancement and hypometabolism on PET scan are atypical for high-grade primary or metastatic brain neoplasms. The radiological differential includes PML or BNS. PML produces a pattern of demyelination that is predominantly localized to the frontal and parieto-occipital lobes. Lesions are generally hypointense and