Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk.

BACKGROUND: Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in AD brain is the result of upregulation of tau kinases and downregulation of tau phosphatases. METHODS: In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk. RESULTS: There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele. CONCLUSION: Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD risk.

Cluster headache: orbital hemodynamic changes during Valsalva maneuver.

BACKGROUND: The clinical features of cluster headache (CH) disclose some vascular changes in the symptomatic region, but few instrumental studies have assessed orbital hemodynamics in patients with this disorder. METHODS: Orbital blood flow reactivity elicited by Valsalva maneuver (VM) was studied with ophthalmic artery eco-Doppler in 16 patients (14 men and 2 women; mean age: 41.2) suffering from episodic CH and in 18 healthy controls. Patients were examined twice: first, in a cluster period (between pain attacks), and second, in a remission period. Each time peak-systolic and end-diastolic flow velocities were recorded in both ophthalmic arteries at rest and during all phases of VM. RESULTS: Valsalva phase IV was consistently associated with an increment of blood flow velocities through the ophthalmic arteries. Unlike controls, patients showed an asymmetric vascular reactivity. In the cluster period peak-systolic flow velocity increments were lower on the symptomatic side than on the asymptomatic side (14.1% vs. 34.4%; P < .001), while in remission end-diastolic flow velocity increments were higher in the previously symptomatic orbit (129% vs. 72.9%; P < .05). Vascular reactivity on the asymptomatic side was always similar to that of healthy controls. CONCLUSIONS: In episodic CH, the symptomatic orbit shows an abnormal vascular reactivity. During the cluster period, basal vasodilation and hyperemia could preclude it from admitting a much greater amount of blood at the end of Valsalva. During remission, there might be some latent vascular changes that lead to supersensitive vasodilator responses and/or opening of arteriovenous shunts under certain circumstances such as Valsalva. These phenomena could be relevant in the pathophysiology of CH.

Nummular headache: a prospective series of 14 new cases.

OBJECTIVE: To study the clinical features of nummular headache (NH) and get an approach to its epidemiology. BACKGROUND: NH has been recently described as a primary disorder characterized by head pain exclusively felt in a small rounded area typically 2-6 cm in diameter. METHODS: Through a 1-year period we have studied all patients referred to our neurologic clinic because of head pain exclusively felt in a small-circumscribed area, and not attributed to another disorder. All the patients had normal neurological, analytical, and neuroimaging examinations. All the patients belonged within the same regional care system comprising 220,000 inhabitants. RESULTS: A total of 11 females and 3 males were studied. Based in our hospital series, the incidence was 6.4/100,000/year. The mean age at the onset was 38 years (range: 13-72). Only three patients had another concurrent headache: migraine (n = 2), and trigeminal neuralgia (n = 1) which proved to have an independent course. All the patients reported head pain exclusively felt in either a rounded (n = 12) of 1-6 cm diameter, or an oval area (n = 2) of 5 x 3 cm, and 2 x 3 cm, respectively. Both size and shape of the painful area remained constant since the onset of symptoms. The location of the symptomatic area was mostly parietal (n = 7) or temporal (n = 5), but also frontal (n = 1) and in occiput (n = 1). The background pain was mostly mild-to-moderate, but also moderate-to-severe pain was reported. Exacerbations-either spontaneous or precipitated by combing hair or touching the symptomatic area-were reported by 8 patients. The temporal pattern was chronic-continuous (n = 7) and episodic (n = 7). Ten patients reported a variable combination of sensory disturbance (tenderness, hypoesthesia, hyperalgesia, and allodynia) in the symptomatic area. There were no autonomic accompaniments. Treatment was generally not necessary. When needed, standard oral doses of paracetamol usually sufficed. CONCLUSIONS: NH emerges as a clear-cut clinical picture. It is a noninfrequent primary headache. The particular topography suggests the pain has a probable epicranial source conveyed by, or originated in, one/a few terminal branch(es) of the cutaneous nerves of the scalp.