Angelo Aliprandi

Increased plasma glutamate in stroke patients might be linked to altered platelet release and uptake

Experimental studies have shown the role of excitotoxicity in the pathogenesis of ischemic brain lesions, and glutamate levels have been found to be elevated in CSF and plasma from patients, early after stroke. In this study, we investigated whether platelets could be involved in the mechanism of altered plasma glutamate levels after stroke. Forty four patients, from 6 hours to 9 months after ischemic stroke, 15 age-related healthy controls and 15 controls with stroke risk factors or previous transient ischemic attack were enrolled. Glutamate plasma levels, platelet glutamate release after aggregation and platelet glutamate uptake were assessed. Plasma glutamate levels were increased up to 15 days after the ischemic event in stroke patients, and the levels at day 3 were inversely correlated with the neurologic improvement between day 3 and 15. Ex vivo platelet glutamate release was decreased by 70% in stroke patients, suggesting previous in vivo platelet activation. Moreover, platelet glutamate uptake in these patients was decreased by 75% up to 15 days and was still reduced 90 days after stroke. Our data show a prolonged increase of glutamate in plasma after stroke, which might presumably be linked to altered platelet functions, such as excessive release of the amino acid or impaired uptake.

Cerebral venous thrombosis

Cerebral venous thrombosis (CVT) was formerly considered a rare disorder, associated with an unfavorable outcome. More recent data based on modern imaging techniques, however, have changed our perception of this disorder. The use of angiography and, especially, MRI have allowed an early diagnosis and have proved that the incidence of CVT is, in fact, higher than previously thought, approximately 3–4 cases per million people per year, and that the majority of patients have a favorable outcome. At present, the most frequent causes are oral contraceptives assumption and pregnancy/puerperium; as a consequence, 75% of patients are females. CVT may cause isolated intracranial hypertension or lead to an ischemic stroke, which does not follow the distribution of an arterial vessel and has a relevant vasogenic edema. Venous strokes often have a hemorrhagic component, ranging from small petechiae to an actual intracerebral hemorrhage; the latter is associated with a worse clinical course. The clinical presentation of CVT is hihgly variable and includes patients with just a mild headache, others with focal neurological deficits and a few with a dramatic syndrome with coma; seizures are a frequent presenting symptom. The best radiological examination to confirm the suspicion of CVT is MRI of the brain, which can both demonstrate parenchymal lesions and directly show evidence of sinus occlusions. The available evidence suggests that anticoagulants are effective in reducing mortality and dependency in CVT patients; the possible role of systemic or localized thrombolysis is still to be established.

Migraine and hypertension

Although the possibility of a comorbidity between migraine and hypertension has long been suspected, the epidemiologic evidence is controversial, with studies demonstrating positive, negative or no correlation between the two diseases. A unifying view that takes into account the most recent evidence suggests that there might be a different effect of diastolic and systolic pressure, with the former having a positive and the latter a negative correlation with migraine. In this paper, the methodologic and clinical reasons for the discrepancies in epidemiologic studies are discussed, together with the possible biological mechanisms that might account for the migraine-hypertension correlation. One such mechanisms may be the renin angiotensin system, which is certainly involved in hypertension and has activities in the CNS that may be relevant for migraine pathogenesis. Despite the uncertainty still present in this field, the control of hypertension in migraine patients is an important factor for the success of migraine treatment and to lower cerebrovascular risk.

Muscle ultrasonography for detecting fasciculations in frontotemporal dementia

Abstract Ultrasound detection of muscle fasciculations was recently proposed for assessing lower motor neuron (LMN) dysfunction in ALS patients. Given the continuum between ALS and frontotemporal degeneration (FTD), the aim of the present study was to evaluate muscle ultrasound (MUS) in FTD both for feasibility and prevalence of fasciculations. Twenty-two FTD patients were examined (five muscles bilaterally: biceps brachii, first dorsalis interosseous, T10 paraspinalis, vastus lateralis, tibialis anterior) with a 7-MHz linear array transducer and a fasciculation score (FS) computed. Twenty-two matched cognitively-intact control subjects and six ALS patients were also included. Results showed that MUS was feasible, reliable and well tolerated in all subjects. Two FTD/MND patients displayed very high FS values, similar to those in ALS patients. The remaining 20 FTD patients displayed a mean FS value significantly higher than the control group with six patients (30%) having FS values out of the range of controls. Disease progression rate correlated with the FS. In conclusion, MUS can be easily applied to FTD patients and represents a non-invasive technique for defining LMN involvement in these patients. LMN dysfunction is a frequent condition in FTD and might identify a subset of patients with a different clinical course.

Paraneoplastic cerebellar degeneration with anti-CV2/CRMP5 antibodies and prostate adenocarcinoma

An 80-year-old male patient, with no relevant previous family and medical history was admitted to our unit for progressive dysarthria, limb and gait ataxia developed during the previous 10 months. Mild axonal sensorimotor polyneuropathy was also present. Brain MR scan disclosed marked shrinkage of the cerebellum and slight atrophy of supratentorial structures. Lumbar puncture and blood tests were not informative. Prostate specific antigen (PSA) was 1220 ng/mL (normal values\4000 ng/mL) and increased values were shown for neuron-specific enolase (NSE, 25.7 lg/L, normal range: 0–12.5; reconfirmed at a subsequent determination); CYFRA 21-1 was negative. A positive title of anti-CV2/CMRP5 antibodies was found in serum samples in two separate occasions by combining indirect immunofluorescence (IFI) and immunoblot techniques (Fig. 1). Serum anti-Hu, -Yo, -Ri, -amphiphysin, and -GAD65 were negative. Total-body FDG-PET scan showed marked hypermetabolism of the prostatic gland. A biopsy detected an adenocarcinoma with no evidence of extracapsular dissemination (Gleason score 3/3). The patient was started on bicalutamide and tamoxifen. Intravenous immunoglobulins (IVIG, 0.4 g/kg/die for 5 days) were then administered with an initial favorable response that eventually disappeared despite a second trial 3 months later. Nine months later ataxia was still severe (Klockgether’s score 27/35, worst items trunk and gait ataxia) [1]. Most of the antibodies found associated with paraneoplastic cerebellar degeneration (PCD) are directed against intracellular antigens either widely expressed in several neuronal types (ANNA), or specifically in Purkinje cells (e.g., PCA-2) [2]. Anti-CV2, also known as antiCRMP5 (Collapsin Response Mediator Protein 5) was initially reported in a patient with cerebellar ataxia, uveitis and peripheral neuropathy associated to breast/undifferentiated carcinoma [3]. A case series of 37 anti-CV2-positive patients was subsequently compared to 324 patients with a positive titre for anti-Hu, with higher rates of cerebellar ataxia and uveo/retinal involvement and lower rates of peripheral neuropathy in the former group with respect to the latter [4]; chorea and myasthenic syndromes were recorded only in the anti-CV2 group, while limbic encephalitis was equally present in the two groups. SCLC was the most frequent cancer in both groups of patients, while malignant thymoma was represented only in the antiCV2 positive group. Interestingly, prostate adenocarcinoma was not reported, while the much more aggressive small cell prostate carcinoma (SCPC) was reported without overt differences between the two groups [4]. Apart from PCD, anti-CV2 has been strongly associated to peripheral neuropathy, as was found for our patient [5]. Paraneoplastic diseases have been reported in association with prostate adenocarcinoma and PCD is listed among possible presentations, implying that this site should be always included in the search for occult malignancies [6]. Furthermore, the possibility of either finding SCPC A. Aliprandi A. Terruzzi A. Rigamonti A. Salmaggi (&) Neurology-Stroke Unit Division, Department of Neuroscience, ‘‘A. Manzoni’’ Hospital, Lecco, Italy e-mail: a.salmaggi@ospedale.lecco.it

Thunderclap headache and benign angiopathy of the central nervous system: a common pathogenetic basis

Thunderclap headache (TCH) is a head pain that begins suddenly and is severe at onset; TCH might be the first sign of different neurological illnesses, and primary TCH is diagnosed when no underlying cause is discovered. Patients with TCH who have evidence of reversible, segmental, cerebral vasoconstriction of circle of Willis arteries and normal or near-normal results on cerebrospinal fluid assessment are thought to have reversible cerebral vasoconstriction syndrome (RCVS). Herein, we discuss the differential diagnosis of TCH and offer pathophysiological considerations for TCH and RCVS.

Donepezil modulates the endogenous immune response: implications for Alzheimer's disease

Donepezil (DNPZ) is a drug commonly used for Alzheimers disease (AD) that may favour a T helper 2 phenotype leading to increased naturally occurring auto‐antibodies (NAb) against beta‐amyloid (Aβ). We hypothesized the involvement of the cholinergic receptors [α7‐nicotnic acetylcholine receptor (α7nAChR)] expressed on peripheral blood mononuclear cells (PBMC).

Dissection of the epiaortic and intracranial arteries

Dissection of epiaortic vessels is a rare event but can have serious clinical consequences such as ischaemic injury to the brain, cerebellum or, more rarely to the retina and is an important cause of stroke in young adults. The main clinical presentation is headache or neck pain, usually but not always associated with Horner syndrome or other local symptoms, followed by an ischemic event in the carotid or vertebral district. Very rarely, the dissection can extend to the intracranial vessels leading to subarachnoid hemorrhage. The time between the headache and the stroke is variable, ranging from a few seconds to weeks. Suspecting an arterial dissection in cases of unexplained head or neck pain in young patients is than crucial to avoid cerebrovascular events; the clinical suspect must be confirmed by ultrasound examination of the epiaortic vessels as a first screening exam, followed by an appropriate neuroimaging study. Treatment with anticoagulants, although not supported by randomized trials, is generally employed to prevent embolic events. The prognosis of stroke caused by arterial dissection does not differ from that of ischaemic events of other origin; the rate of recurrence is low and most patients have only one event in their live. Clinical research with multicenter recruitment is ongoing to provide more solid evidence on the management and prognosis of arterial dissections.

Alterations in the cerebral venous circulation as a cause of headache

The alterations of the cerebral venous circulation are a rare but clinically important cause of headache. Although any process involving the cerebral veins or sinuses may cause headache, the most frequent and important are cerebral venous thrombosis and idiopathic intracranial hypertension. The headache of cerebral venous thrombosis does not have specific features and may be isolated; therefore, all patients with headache and risk factors for venous thrombosis should undergo the appropriate neuroradiologic examinations to rule out the diagnosis. In fact, early anticoagulant treatment may dramatically change the clinical outcome. Also idiopathic intracranial hypertension, if untreated, may have serious clinical consequences such as permanent visual loss. The pathogenesis of this disorder has not been clearly established and several possibilities involving the cerebral circulation are discussed.

MIDAS questionnaire in the emergency setting

Abstract.Migraine is a common disorder and is a major cause of disability and loss of working performance in western countries. Therefore, many tools have been developed to assess migraine related disability. Among these, the Migraine Disability Assessment (MIDAS) questionnaire has been shown to be of particular interest, as it is valid, reliable and useful for therapeutic decisions. In this pilot study, we address the validity of the MIDAS questionnaire in an unselected population of migraine patients in the emergency setting. We found that the MIDAS scores in the emergency room were similar to those collected in a specialised headache centre. This result suggests that the MIDAS questionnaire could be reliably used in the emergency setting, hence avoiding unnecessary delays in the treatment of migraine patients.