Alternating hemiplegia of childhood.

Alternating hemiplegia of childhood (AHC) is characterized by recurrent episodes of hemiplegia which may alternate sides between attacks. The condition is associated with severe neurodevelopmental disorder presenting in early infancy, and may encompass a wide range of other paroxysmal manifestations (e.g., dystonia, nystagmus, dysautonomia) and pervasive neurological disabilities (e.g., developmental delay, learning disabilities, choreoathetosis, and ataxia). Epileptic seizures are particularly common among patients with AHC. Diagnosis is usually based on history and clinical grounds using the Aicardi criteria. Mutations in the ATP1A3 gene are implicated in the disease pathology of the condition, as well as several other neurodevelopmental disorders, suggesting AHC forms part of a spectrum of overlapping clinical syndromes rather than a distinct clinical entity per se. Management of patients with AHC includes the rapid induction of sleep during paroxysmal attacks and the avoidance of identified triggers. Pharmacotherapeutic treatments have a role in managing epileptic seizures, as well as in the prevention of paroxysmal attacks wherein flunarizine remains the treatment of choice.

Association of Clinical and Neuroanatomic Factors With Response to Ventral Tegmental Area DBS in Chronic Cluster Headache.

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) of the ventral tegmental area (VTA) is a surgical treatment option for selected patients with refractory chronic cluster headache (CCH). We aimed to identify clinical and structural neuroimaging factors associated with response to VTA DBS in CCH. METHODS: This prospective observational cohort study examines consecutive patients with refractory CCH treated with VTA DBS by a multidisciplinary team in a single tertiary neuroscience center as part of usual care. Headache diaries and validated questionnaires were completed at baseline and regular follow-up intervals. All patients underwent T1-weighted structural MRI before surgery. We compared clinical features using multivariable logistic regression and neuroanatomic differences using voxel-based morphometry (VBM) between responders and nonresponders. RESULTS: Over a 10-year period, 43 patients (mean age 53 years, SD 11.9), including 29 male patients, with a mean duration of CCH 12 years (SD 7.4), were treated and followed up for at least 1 year (mean follow-up duration 5.6 years). Overall, there was a statistically significant improvement in median attack frequency from 140 to 56 per month (Z = -4.95, p < 0.001), attack severity from 10/10 to 8/10 (Z = -4.83, p < 0.001), and duration from 110 to 60 minutes (Z = -3.48, p < 0.001). Twenty-nine (67.4%) patients experienced ≥50% improvement in attack frequency and were therefore classed as responders. There were no serious adverse events. The most common side effects were discomfort or pain around the battery site (7 patients) and transient diplopia and/or oscillopsia (6 patients). There were no differences in demographics, headache characteristics, or comorbidities between responders and nonresponders. VBM identified increased neural density in nonresponders in several brain regions, including the orbitofrontal cortex, anterior cingulate cortex, anterior insula, and amygdala, which were statistically significant (p < 0.001). DISCUSSION: VTA DBS showed no serious adverse events, and, although there was no placebo control, was effective in approximately two-thirds of patients at long-term follow-up. This study did not reveal any reliable clinical predictors of response. However, nonresponders had increased neural density in brain regions linked to processing of pain and autonomic function, both of which are prominent in the pathophysiology of CCH.