Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis.

Accurate prediction of neurological outcome in survivors of cardiac arrest may be difficult. We report the case of a 44-year-old survivor of a hypoxic cardiac arrest who repeatedly developed relentless myoclonic jerks on attempted discontinuation of his propofol infusion. These were initially thought to represent myoclonic status epilepticus before the correct diagnosis of Lance-Adams syndrome was made. Lance-Adams syndrome is a rare disorder seen in survivors of profound hypoxic episodes. It is characterised by intention myoclonus but preserved intellect. Accurate distinction between myoclonic status epilepticus and Lance-Adams syndrome is vital as they have very different prognoses. The different pathophysiology and distinguishing clinical features of these two conditions are highlighted.

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients.

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO(x)) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NO(x) values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO(x) excretion between control and migraine populations, the variable temporal association of NO(x) peaks and headaches suggests a complex role of NO in this condition.

Diffusion- and perfusion-weighted MR imaging in persistent migrainous visual disturbances.

Pathological changes on diffusion-weighted MR scans had been described in hemiplegic migraine and perfusion changes had been demonstrated in typical migraine aura with radio-isotope studies and, more recently, MR perfusion imaging. However, there is relatively little knowledge of the pathophysiology of long-lasting migraine aura and its possibly variant phenotype, visual snow. Our aim was to investigate with advanced MR techniques whether patients with long-lasting visual disturbance showed regional alterations in cerebral water diffusion and perfusion. We have studied four patients using MR perfusion and MR diffusion imaging. Two patients had typical visual aura and two had a primary persistent visual disturbance (visual snow phenomenon). All patients had normal conventional structural MR imaging. MR diffusion-weighted images were acquired with a b-value of up to 1000 s/mm2. From the diffusion weighted images we generated maps of apparent diffusion coefficient (ADC), which were inspected visually and used for ADC measurements of predefined regions of interest, which included the visual, frontal, insular and temporal cortices. MR perfusion imaging was performed using a bolus tracking technique with dynamic susceptibility-weighted images. Colour coded maps of relative cerebral blood volume, mean transit time and bolus arrival time were generated, as well as time-signal intensity curves over the anterior, middle and posterior cerebral artery territories. The maps of the ADC and above perfusion parameters appeared symmetrical in all patients with no evidence of decreased water diffusion or cerebral perfusion in the occipital regions, or elsewhere. There was no statistically significant difference between the ADC measurements of the primary visual cortices and other cortical regions. Our findings suggest that regional changes in cerebral water diffusion and perfusion do not play an important part in the pathophysiology of persistent migraine aura or primary persistent visual disturbance.

The effect of multiple stimuli on the modulation of the 'nociceptive' blink reflex.

The 'nociceptive' blink reflex is a method of examining human trigeminal pain pathways. We explored temporal summation of this reflex by using a train of pulses, rather than a single pulse, and remote activation of diffuse noxious inhibitory control (DNIC), to improve reliability, flexibility and nociceptive specificity of this technique. The R2 component of the nociceptive blink reflex response (nR2) was assessed in 28 healthy volunteers using between 1 and 7 pulses per stimulus train (inter-pulse interval 5 ms). The effect of DNIC on single-, double-, and triple-pulse nR2 was investigated. Compared to single pulses, double and triple pulses increased the sensation of pain, reduced the tactile and pain thresholds, and facilitated the blink reflex responses (reduced onset latency, increased magnitude and persistence of nR2). The maximal reflex facilitation was achieved using a triple pulse. Higher pulse numbers had no additional facilitatory effect. Activation of the DNIC system using heterotopic pain suppressed the nR2 evoked by double and triple stimulation by 16 and 42%, respectively, but not the nR2 from a single pulse. Stimulation with double and triple pulses may be more suitable to study influences on nociceptive pathways than single pulses and may widen the methodological flexibility of the nociceptive blink reflex technique. This technique may be useful in studying the trigeminal nociceptive system with particular reference to primary headache disorders and their neuropharmacology.

Nociceptive-specific blink reflex and glyceryl trinitrate infusion in healthy volunteers.

Glyceryl trinitrate (GTN) is known to induce early headache in healthy humans after intravenous infusion. Moreover, in animal models subcutaneous administration produces an increase in Fos expression in brainstem areas that are involved in trigeminal pain processing. In a double-blind crossover study, we tested the blink reflex before, during and immediately after GTN and placebo intravenous infusion in eight healthy volunteers using a new stimulation electrode that preferentially activates A-delta nociceptive afferent fibres. The initial hypothesis that GTN could induce an increase in the magnitude of the nociceptive blink reflex R2 component by stimulating activity of trigeminal nucleus caudalis wide dynamic range interneurones was not confirmed. Although mild headache was induced in six subjects, there was no significant change between the R2 area under the curve before and after drug vs. placebo.

Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine.

BACKGROUND: Familial hemiplegic migraine (FHM) is a rare autosomal dominant subtype of migraine with aura. Missense mutations in the chromosome 19 CACNA1A calcium channel gene have been found in approximately half of the families. The T666M mutation, replacing a threonine by a methionine at residue number 666, is the most frequent mutation, reported in 14 independent FHM families; other mutations have so far been described in only 1 or 2 families each. The clinical features of T666M families have been reported, but the course is unknown. OBJECTIVE: To present a detailed description of the clinical features of new FHM families in which we identified the T666M mutation in our CACNA1A screening program. METHODS: As part of our ongoing genetic screening, mutation analysis of the CACNA1A gene was performed by single-strand conformational polymorphism analysis in 33 probands of families with FHM. RESULTS: We identified the T666M mutation in 5 unrelated FHM families. In 3 of the families, patients displayed cerebellar ataxia. In 1 family, some affected members with the mutation had attacks with confusion but without hemiparesis. In 1 family, patients had progressive cognitive dysfunction. CONCLUSIONS: The T666M mutation is the most frequent CACNA1A mutation in FHM; it was found in 5 of 33 FHM families at our laboratory, and in 19 of 39 families with a known mutation reported in the literature (including the present study). Screening for the T666M mutation should therefore be the first step when screening families with FHM. There is a remarkable clinical heterogeneity among families with the T666M mutation.

Effect of the adenosine A1 receptor agonist GR79236 on trigeminal nociception with blink reflex recordings in healthy human subjects.

GR79236 is a highly potent and selective adenosine A1 receptor agonist that has analgesic and anti-inflammatory actions in humans and animals. In animal models it inhibits trigeminal nerve firing and calcitonin gene-related peptide release which play a pivotal role in migraine pathophysiology. Thus GR79236 may have therapeutic potential in migraine. Although there are no validated human models of migraine, the trigeminal nociceptive pathways may be studied with a novel electrode to elicit nociception-specific blink reflex responses. Twelve healthy female volunteers were randomized in a double-blind, placebo-controlled, cross-over trial to investigate the effect of GR79236 on trigeminal nociceptive pathways, as measured by the blink reflex. A secondary objective was to compare the use of two types of electrode, the standard (SE) and nociception-specific electrodes (NE), to investigate human trigeminal pharmacology. Blink reflexes were elicited with SE and NE before and 30 min after GR79236 (10 microg/kg i.v.) or placebo. The median area under the curve of repeated sweeps of the R2 component of the blink reflex was analysed using analysis of covariance with baseline as covariate. Using NE, GR79236 produced a non-significant reduction of the ipsilateral R2 compared with placebo (P = 0.097) and a significant reduction contralaterally (P = 0.008). No significant changes were observed using SE. There were no significant adverse events. The results suggest that NE is more sensitive than SE to detect pharmacological effects in the trigeminal nociceptive system. Furthermore, the adenosine A1 receptor agonist GR79236 inhibits trigeminal nociception in humans. These results support a possible therapeutic role for GR79236 in primary headache disorders.

Premonitory symptoms in migraine: an electronic diary study.

BACKGROUND: Migraine is frequently associated with nonheadache symptoms before, during, and after the headache. Premonitory symptoms occurring before the attack have not been rigorously studied. Should these symptoms accurately predict headache, there are considerable implications for the pathophysiology and management of migraine. METHODS: Electronic diaries were used in a 3-month multicenter study to record nonheadache symptoms before, during, and after migraine. The authors recruited subjects who reported nonheadache symptoms in at least two of three attacks that they believed predicted headache. Symptoms were entered in the diaries by patient initiation and through prompted entries at random times daily. Entries could not be altered retrospectively. Data recorded included nonheadache symptoms occurring during all three phases of the migraine, prediction of the attack from premonitory symptoms, general state of health, and action taken to prevent the headache. RESULTS: One hundred twenty patients were recruited: 97 provided usable data. Patients correctly predicted migraine headaches from 72% of diary entries with premonitory symptoms. A range of cognitive and physical symptoms was reported at a similar rate through all three phases of the migraine. The most common premonitory symptoms were feeling tired and weary (72% of attacks with warning features), having difficulty concentrating (51%), and a stiff neck (50%). Subjects who functioned poorly in the premonitory phase were the most likely to correctly predict headache. CONCLUSIONS: Using an electronic diary system, the authors show that migraineurs who report premonitory symptoms can accurately predict the full-blown headache.

Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A mutation.

Benign paroxysmal torticollis of infancy (BPTI) is a disorder characterized by recurrent episodes of head tilt secondary to cervical dystonia. Attacks are often accompanied by vomiting, pallor, and ataxia, settling spontaneously within hours or days. Episodes begin within the first 12 months of life and resolve by 5 years. We report four patients with BPTI. Symptoms started from 3 months of age, with head tilting lasting between 10 minutes and 2 months; the shorter episodes were followed by vomiting, apathy, and unsteadiness. Head tilt became less prominent after infancy, replaced by vertigo and eventually by migraine headaches. Two patients came from a kindred with familial hemiplegic migraine linked to CACNA1A mutation. BPTI may be regarded as a migraine aura equivalent. The syndrome poses interesting questions regarding varying phenotypic expression of calcium channelopathies at different stages of development.

Basilar artery aneurysm with autonomic features: an interesting pathophysiological problem.

Unruptured cerebral aneurysms often present with neuro-ophthalmological symptoms but ocular autonomic involvement from an aneurysm of the posterior circulation has not previously been reported. A patient is described with a basilar artery aneurysm presenting with headache and unilateral autonomic symptoms. After angiographic coiling of the aneurysm there was a near complete resolution of these features. The relevant anatomy and proposed mechanism of autonomic involvement of what may be considered--from a pathophysiological perspective as a secondary trigeminal-autonomic cephalgia--is discussed