Predictive role of presenting symptoms and clinical findings in idiopathic intracranial hypertension.

BACKGROUND: The aim of the study was to evaluate the presenting symptoms and signs of idiopathic intracranial hypertension (IIH) in a large cohort of patients and to estimate their possible role in establishing the diagnosis of IIH. METHODS: This prospective cohort study in two tertiary centers, the Danish Headache Center in Rigshospitalet-Glostrup and the Neurology Clinic of the Clinical Center of Serbia, included 286 patients referred by attending specialists for possible IIH evaluation. Patients were divided into two groups: one with confirmed IIH diagnosis and one with rejected IIH diagnosis. RESULTS: The diagnosis of IIH was confirmed in 219 (76.6%) patients. It was more often confirmed if the patient was referred by an ophthalmologist than if the referral was from a neurologist (83.6% vs. 69.8%, p = .029) and in patients with higher body mass index (BMI) (p = .032). Transient visual obscurations (p = .006), double vision (p = .033), neck pain (p = .025), and tinnitus (p = .013) were presenting symptoms more frequently reported by patients with IIH diagnosis. In the same group of patients, papilledema (p < .001) and sixth nerve palsy (p = .010) were noted significantly more often. Papilledema was extracted by multivariate analysis as an independent predictor of IIH diagnosis (p < .001). CONCLUSION: Although studies investigating IIH report an abundance of presenting symptoms, our results indicate that these symptoms are not diagnostic for IIH. Papilledema is the most reliable clinical sign predicting the correct IIH diagnosis in patients with suspected IIH.

Idiopathic intracranial hypertension from the perspective of headache center.

Idiopathic intracranial hypertension (IIH) is a pathological state defined as an increase of intracranial pressure in the absence of a causative pathological process. The aim of this study was to evaluate the clinical features of the patients with IIH diagnosed in our Headache Center according to the current knowledge of this disorder. In the retrospective and cross-sectional analysis of 3395 patients we present 12 newly diagnosed IIH patients, ten women and two men, aged from 19 to 51, with obtained values of cerebrospinal fluid pressure between 250 and 680 mm of water. The symptoms of IIH clinical presentation have been headache, reported by 92% of patients; papilledema, noted in 67%; and cranial nerve impairment (25%). The results obtained from presented patients confirmed the presence of headache features that are included in criteria for headache attributed with IIH in majority of them: progressive, daily, diffuse, non-pulsatile headache with aggravation by coughing or straining. Decrease of pain intensity after lumbar puncture was noted in all patients. We notice the relatively small proportion of patients with headache attributed to IIH among the patients treated in our Headache Center. The prevalence of IIH is not low and headache is the most frequent presenting symptom; therefore, we could only conclude that some chronic headache patients refractory for treatment are patients with IIH.

Skin and sural nerve biopsies: ultrastructural findings in the first genetically confirmed cases of CADASIL in Serbia.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited vascular disorder caused by Notch3 gene mutations. The main histopathological hallmark is granular osmiophilic material (GOM) deposited in the close vicinity of vascular smooth muscle cells (VSMCs). The authors report the first 7 ultrastructurally and genetically confirmed cases of CADASIL in Serbia. Samples of skin and sural nerve were investigated by transmission electron microscopy. GOM deposits were observed around degenerated VSMCs in all the skin biopsies examined. Sural nerve biopsies revealed severe alterations of nerve fibers, endoneurial blood vessels with GOM deposits, endoneurial fibroblasts, and perineurial myofibroblasts. Total genomic DNA was extracted from peripheral blood leukocytes, and exons 2-6 of the Notch3 gene were amplified by PCR and subsequently sequenced. Four different mutations in exons 2 (Cys65Tyr), 3 (Gly89Cys and Arg90Cys), and 6 (Ala319Cys), which determine the CADASIL disease, were detected among all described patients. A novel missense mutation Gly89Cys involving exon 3 was detected. Due to the difficulties in the determination of the Notch3 mutations, these data suggest that electron microscopic analysis for GOMs in dermal vessel wall provides a rapid and reliable screening method for this disease.

What are the differences between younger and older patients with symptomatic small vessel disease?

OBJECTIVE: Although typically linked to aging, small vessel disease (SVD) is also observed in younger adult patients, with common vascular risk factors (RF). We aimed to investigate features of SVD occurrence at an early adult age. PATIENTS AND METHODS: Vascular RF, functional and cognitive status and severity of lesions on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale were analyzed in 200 consecutive patients with cerebral SVD admitted to a tertiary neurological hospital. Variables were compared between younger (35-55 years) and older (>56 years) patients. RESULTS: In this study, 63 (31.5%) of patients were 55 years or younger. Both age groups had comparable RF profiles, but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9; 95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI 1.3-2.5; p=0.0001) and cognitive (χ(2) 13.94; p=0.0009) status compared to older patients. However, two thirds of younger patients had some degree of cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean 12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There was a strong correlation in both groups between functional score, cognitive status and ARWMC score (p<0.0001). CONCLUSION: In our dataset, younger patients with SVD shared common vascular RF with older patients. In the group aged ≤55, better functional and cognitive status and less severe MRI changes were noted. However, a substantial number of younger SVD patients presenting with TIA or ischemic stroke had various deficits.

Comorbidities in cluster headache and migraine.

The aim of this study was to investigate the most frequent comorbid diseases occurring in patients with cluster headache (CH) and, for comparison, in migraine patients. Over a period of eight years 130 patients with CH and 982 patients with migraine were diagnosed according to ICHD-II criteria. In all patients the presence and type of different diseases were assessed from medical records and coded by the ICD, X revision. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were calculated by logistic regression analyses. Comorbid disorders were present in 56.9% patients with CH and in 56.7% migraine patients. Chronic sinusitis (p = 0.001), malignancy (p = 0.012), diabetes mellitus (p = 0.021), glaucoma (p = 0.038), as well as another primary headache disorders were more frequently present in patients with cluster headache (p = 0.001), than in migraine patients. In the multivariate analysis, chronic sinusitis (OR = 7.6, p = 0.001) and diabetes mellitus (OR = 4.2, p = 0.035), adjusted by gender, age and duration of headache, are more frequently associated with CH than with migraine. Comorbid disorders in CH patients were frequent and similar to those noticed in migraine patients, except chronic sinusitis and diabetes mellitus.

Bilateral SUNCT-like headache in a patient with prolactinoma responsive to lamotrigine.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome is a rare trigeminal autonomic cephalalgia. The cases of SUNCT with attacks that affected both sides simultaneously have only rarely been reported and some of them had underlying pathology. We have reported a case of bilateral SUNCT-like headache secondary to a prolactinoma and responsive to lamotrigine treatment.

Etiology of ischemic stroke among young adults of Serbia.

BACKGROUND/AIM: Etiology of ischemic stroke (IS) among young adults varies among countries. The aim of the study was to investigate the causes and risk factors of IS in the young adults of Serbia. METHODS: A total of 865 patients with IS, aged 15 to 45 years, were treated throughout the period 1989-2005. Etiologic diagnostic tests were performed on the patient by the patient basis and according to their availability at the time of investigation. The most likely cause of stroke was categorized according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. RESULTS: There were 486 men and 379 women, with 19% of the patients < or = 30 years old. Large artery arteriosclerosis and small artery disease were confirmed in 14% of the patients, and embolism and other determined causes in 20%. Undetermined causes made up 32% of the patients, mostly those (26%) with incomplete investigations. Smoking (37%), hypertension (35%) and hyperlipidemia (35%) were the most common risk factors. Rheumatic heart diseases and prosthetic valves were the most common causes of IS. Arterial dissections and coagulation inhibitors deficiency were detected in a small number of patients. CONCLUSION: Etiology of IS among Serbian young adults shares characteristics of those in both western and less developed countries.

[Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)--three case reports from Serbia].

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy leading to recurrent strokes and vascular dementia in young and middle-aged patients. The diagnosis of CADASIL is based on typical clinical presentation and characteristic magnetic resonance imaging (MRI) changes, and has to be confirmed by biopsy of the sural nerve, muscle and skin, as well as by genetic analysis. Mutations within the Notch3 gene were identified as the underlying genetic defect in CADASIL. CASE OUTLINE: The clinical manifestations of the first presented patient with migraine from the age of thirteen, stroke without vascular risk factors and stepwise progression of vascular dementia comprising the typical clinical picture of CADASIL, were confirmed after seven years with pathological verification. The second presented case did not satisfy the clinical criteria for CADASIL. His stroke was considered to be related with vascular risk factors--diabetes mellitus and hypertension. The aetiological diagnosis was established only when his brother without vascular risk factors presented with similar clinical manifestations. CONCLUSION: Until the development of the new neuroimaging techniques like MRI, pathologic and genetic analysis, CADASIL was considered as a rare disorder. However, the increasing number of CADASIL families has been identified throughout the world showing that this entity is usually underdiagnosed. This article presents three patients from two Serbian families with clinical suspicion of CADASIL verified by pathologic examination.

Cerebral small vessel disease in pseudoxanthoma elasticum: three cases.

BACKGROUND: Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones. CASE DESCRIPTIONS: Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI. DISCUSSION: We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.