Status migrainosus.

Status migrainosus is one of the recognized complications of migraine with or without aura, defined as a persistent debilitating migraine attack lasting for more than 72h with little reprieve, leading to functional disability. The individual impact of status migrainosus and the substantial healthcare burden are highlighted. Current case series which inform our understanding of this condition are examined with two groups emergent, those with classic status migrainosus and those with episodic status migrainosus. The question as to whether status migrainosus is a distinct biological state beyond the established migraine pathophysiology is examined. With the underlying pathophysiology not fully understood, attention is turned to therapeutic considerations and the available evidence informing practice. A practical approach to treatment of status migrainosus is presented. Given the severity and need for emergency care, options detailed are in line with recommendations for acute migraine care: with a staged approach initially combining subcutaneous sumatriptan with parenteral options including dopamine receptor antagonists, nonsteroidal anti-inflammatories and acetaminophen. The place of combination treatment with parenteral magnesium sulfate, dihydroergotamine, antiepileptics, corticosteroids, and anesthetic agents is outlined. With a paucity of high-quality evidence to consolidate current clinical approaches, consideration of future therapies and research questions is raised.

Spontaneous intracranial hypotension.

Spontaneous intracranial hypotension (SIH) is a highly disabling but treatable secondary cause of headache. Recent progress in neuroradiological techniques has catalysed understanding of its pathophysiological basis and clinical diagnosis, and facilitated the development of more effective investigation and treatment methods. A UK-based specialist interest group recently produced the first multidisciplinary consensus guideline for the diagnosis and treatment of SIH. Here, we summarise a practical approach to its clinical and radiological diagnosis, symptomatic and non-targeted interventional treatment, radiological identification of leak site and targeted treatment of the leak once it has been localised.

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.

An open-label observational study and meta-analysis of non-invasive vagus nerve stimulation in medically refractory chronic cluster headache.

Background: Many patients with cluster headache (CH) are inadequately controlled by current treatment options. Non-invasive vagus nerve stimulation (nVNS) is reported to be effective in the management of CH though some studies suggest that it is ineffective. Objective: To assess the safety and efficacy of nVNS in chronic cluster headache (CCH) patients. Method: We prospectively analysed data from 40 patients with refractory CCH in this open-label, observational study. Patients were seen in tertiary headache clinics at the National Hospital for Neurology and Neurosurgery and trained to use nVNS as preventative therapy. Patients were reivewed at one month and then three-monthly from onset. The primary endpoint was number of patients achieving ≥50% reduction in attack frequency at 3 months. A meta-analysis of all published studies evaluating the efficacy of nVNS in CCH was also conducted. We searched MEDLINE and EMBASE for all studies investigating the use of nVNS as a preventive or adjunctive treatment for CCH with five or more participants. Combined mean difference and responder proportions with 95% confidence intervals (CI) were calculated from the included studies. Results: 17/40 patients (43%) achieved ≥50% reduction in attack frequency at 3 months. There was a significant reduction in monthly attack frequency from a baseline of 124 (±67) attacks to 79 (±63) attacks in month 3 (mean difference 44.7; 95% CI 25.1 to 64.3; p < 0.001). In month 3, there was also a 1.2-point reduction in average severity from a baseline Verbal Rating Scale of 8/10 (95% CI 0.5 to 1.9; p = 0.001). Four studies, along with the present study, were deemed eligible for meta-analysis, which showed a responder proportion of 0.35 (95% CI 0.07 to 0.69, n = 137) and a mean reduction in headache frequency of 35.3 attacks per month (95% CI 11.0 to 59.6, n = 108), from a baseline of 105 (±22.7) attacks per month. Conclusion: This study highlights the potential benefit of nVNS in CCH, with significant reductions in headache frequency and severity. To better characterise the effect, randomised sham-controlled trials are needed to confirm the beneficial response of VNS reported in some, but not all, open-label studies.

Speech Registration in Symptomatic Memory Impairment.

Background: An inability to recall recent conversations often indicates impaired episodic memory retrieval. It may also reflect a failure of attentive registration of spoken sentences which leads to unsuccessful memory encoding. The hypothesis was that patients complaining of impaired memory would demonstrate impaired function of "multiple demand" (MD) brain regions, whose activation profile generalizes across cognitive domains, during speech registration in naturalistic listening conditions. Methods: Using functional MRI, brain activity was measured in 22 normal participants and 31 patients complaining of memory impairment, 21 of whom had possible or probable Alzheimer's disease (AD). Participants heard a target speaker, either speaking alone or in the presence of distracting background speech, followed by a question to determine if the target speech had been registered. Results: Patients performed poorly at registering verbal information, which correlated with their scores on a screening test of cognitive impairment. Speech registration was associated with widely distributed activity in both auditory cortex and in MD cortex. Additional regions were most active when the target speech had to be separated from background speech. Activity in midline and lateral frontal MD cortex was reduced in the patients. A central cholinesterase inhibitor to increase brain acetylcholine levels in half the patients was not observed to alter brain activity or improve task performance at a second fMRI scan performed 6-11 weeks later. However, individual performances spontaneously fluctuated between the two scanning sessions, and these performance differences correlated with activity within a right hemisphere fronto-temporal system previously associated with sustained auditory attention. Conclusions: Midline and lateralized frontal regions that are engaged in task-dependent attention to, and registration of, verbal information are potential targets for transcranial brain stimulation to improve speech registration in neurodegenerative conditions.

Neural Systems Involved When Attending to a Speaker.

Remembering what a speaker said depends on attention. During conversational speech, the emphasis is on working memory, but listening to a lecture encourages episodic memory encoding. With simultaneous interference from background speech, the need for auditory vigilance increases. We recreated these context-dependent demands on auditory attention in 2 ways. The first was to require participants to attend to one speaker in either the absence or presence of a distracting background speaker. The second was to alter the task demand, requiring either an immediate or delayed recall of the content of the attended speech. Across 2 fMRI studies, common activated regions associated with segregating attended from unattended speech were the right anterior insula and adjacent frontal operculum (aI/FOp), the left planum temporale, and the precuneus. In contrast, activity in a ventral right frontoparietal system was dependent on both the task demand and the presence of a competing speaker. Additional multivariate analyses identified other domain-general frontoparietal systems, where activity increased during attentive listening but was modulated little by the need for speech stream segregation in the presence of 2 speakers. These results make predictions about impairments in attentive listening in different communicative contexts following focal or diffuse brain pathology.

Fractionating the default mode network: distinct contributions of the ventral and dorsal posterior cingulate cortex to cognitive control.

The posterior cingulate cortex (PCC) is a central part of the default mode network (DMN) and part of the structural core of the brain. Although the PCC often shows consistent deactivation when attention is focused on external events, anatomical studies show that the region is not homogeneous, and electrophysiological recordings in nonhuman primates suggest that it is directly involved in some forms of attention. We report a functional magnetic resonance imaging study of an attentionally demanding task (either a zero- or two-back working memory task). Standard subtraction analysis within the PCC shows a relative deactivation as task difficulty increases. In contrast, a dual-regression functional connectivity analysis reveals a clear dissociation between ventral and dorsal parts of the PCC. As task difficulty increases, the ventral PCC shows reduced integration within the DMN and less anticorrelation with the cognitive control network (CCN) activated by the task. The dorsal PCC shows an opposite pattern, with increased DMN integration and more anticorrelation. At rest, the dorsal PCC also shows functional connectivity with both the DMN and attentional networks. As expected, these results provide evidence that the PCC is involved in supporting internally directed thought, as the region is more highly integrated with the DMN at low task demands. In contrast, the task-dependent increases in connectivity between the dorsal PCC and the CCN are consistent with a role for this region in modulating the dynamic interaction between these two networks controlling the efficient allocation of attention.

MR volume of the fetal cerebellum in relation to growth.

PURPOSE: To quantify fetal cerebellar growth by measuring cerebellar volumes of normal fetuses throughout gestation with MRI. MATERIALS AND METHODS: A total of 93 fetuses with normal brains ranging in age from 16 to 40 gestational weeks were included in the study. Standard fetal biometric measurements were made on a three-dimensional postprocessing workstation and included the head circumference, transverse cerebellar diameter, biparietal diameter, occipital-frontal diameter, as well as cerebellar volume. The gestational ages were estimated from fetal head circumference measurements. Regression analysis was used to find the best-fit model. RESULTS: There is a strong correlation describing cerebellar volume and gestational age in fetuses with normal central nervous systems. A second-order polynomial regression model was found to be the most appropriate descriptor of cerebellar volume in relation to normal fetal growth. In addition, the cerebellar volume was also found to correlate strongly with the common fetal biometric measurements of transverse cerebellar diameter, biparietal diameter, and occipital-frontal diameter. CONCLUSION: Nomograms for fetal cerebellar volume with gestational age derived from head circumference measurements are presented for the first time with MRI. A normal fetal cerebellar volume growth chart is established. These results should prove helpful in defining situations of abnormal growth development and dysmorphology.