BACKGROUND Case reports of subacute sclerosing panencephalitis (SSPE) in individuals with human immunodeficiency virus (HIV) infection are scarce, and the natural history is unclear. To our knowledge, a fulminant present...BACKGROUND Case reports of subacute sclerosing panencephalitis (SSPE) in individuals with human immunodeficiency virus (HIV) infection are scarce, and the natural history is unclear. To our knowledge, a fulminant presentation has not yet been described. OBJECTIVE To describe a case of fulminant SSPE in an individual with a perinatally acquired HIV infection. DESIGN Case report and literature review. SETTING Christian Medical College Hospital, Vellore, India. PATIENT A 17-year-old boy with a perinatally acquired HIV infection. RESULTS The patient presented with subacute-onset cognitive decline and myoclonic jerks with rapid deterioration of health (the patient died within 12 weeks of onset). The findings from magnetic resonance imaging and electroencephalography and the cerebrospinal fluid and serum measles antibody titers were suggestive of SSPE. The fulminant presentation in this case needs to be noted. CONCLUSIONS Along with the better life expectancy of HIV-infected individuals, there may be an increase in the incidence of SSPE in this population. Fulminant SSPE may be added to the spectrum of measles-associated neurological disorders in HIV.
OBJECTIVES: To describe a case and review literature for intracerebral hemorrhage caused by migraine. DESIGN: Case report. SETTING: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. PAT...OBJECTIVES: To describe a case and review literature for intracerebral hemorrhage caused by migraine. DESIGN: Case report. SETTING: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. PATIENT: A 54-year-old truck driver with a 2-year history of atypical headaches. RESULTS: A 54-year-old right-handed truck driver was seen in consultation with a 2-year history of atypical headaches.The headaches were dull, throbbing, gradually progressive,and limited over the left occipital area. They were accompanied by right visual field deficit, diplopia, and,at times, confusion. These headaches were notably different from the usual migraine headaches he had been having for more than 20 years. Brain imaging revealed left parieto-occipital lobar hemorrhage. Further investigations ruled out arteriovenous malformations. He did not have any vascular risk factors, including hypertension. Migraine-associated intracerebral hemorrhage was considered to be the most likely diagnosis. CONCLUSIONS: Intracerebral hemorrhage associated with migraine is believed to result from vasoconstriction leading to ischemia of the walls of blood vessels, making them leaky and porous. It is important to be aware of this phenomenon because vasoactive medications used to treat migraine can further aggravate the vasoconstriction and hence the intracerebral bleed.
Arch Neurol
· 2012 Nov · PMID 22926050
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OBJECTIVE: To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS). DESIGN: Retrospective, cross-sectional cohort study. SETTING: Academic MS center. PATIENTS...OBJECTIVE: To contrast differences in pain and treatment outcomes between neuromyelitis optica (NMO) and multiple sclerosis (MS). DESIGN: Retrospective, cross-sectional cohort study. SETTING: Academic MS center. PATIENTS: Complete ascertainment of an academic MS center cohort of NMO and an MS comparison sample cohort. MAIN OUTCOME MEASURES: Current pain was quantified by a 10-point scale and the McGill Pain Questionnaire.Expanded Disability Status Scale score and number of involved spinal cord levels were collected in addition to testing for cognition, fatigue, depression, and quality of life. Number and types of pain medications were tabulated. RESULTS: Current pain was more common in subjects with NMO (n=29) vs MS (n=66) (86.2% vs 40.9%; P.001)and more severe on a 10-point scale (5.38 vs 1.85;P.001). Pain remained more common after controlling for disability and number of spinal cord segments(P=.03). Prescription pain medication was used more frequently in subjects with NMO compared with subjects with MS(75.9% vs 37.8%; P.001), often requiring more than 1 medication (65.5% vs 15.2%; P.001). No subject with NMO taking pain medication (22 of 29) rated their current pain as 0 of 10, whereas almost half of those taking pain medication with MS were currently free of pain (0% vs 48%; P=.006). CONCLUSIONS: Neuromyelitis optica is frequently associated with severe pain that appears insufficiently controlled by pharmacologic interventions. Future studies should evaluate the efficacy of a multidisciplinary and multimodal approach to pain management.
Hall S, Öhrfelt A, Constantinescu R
… +14 more, Andreasson U, Surova Y, Bostrom F, Nilsson C, Håkan W, Decraemer H, Någga K, Minthon L, Londos E, Vanmechelen E, Holmberg B, Zetterberg H, Blennow K, Hansson O
OBJECTIVE: To assess the ability of 5 cerebrospinal fluid(CSF) biomarkers to differentiate between common dementia and parkinsonian disorders. DESIGN: A cross-sectional, clinic-based study. PARTICIPANTS: Cerebrospinal fl...OBJECTIVE: To assess the ability of 5 cerebrospinal fluid(CSF) biomarkers to differentiate between common dementia and parkinsonian disorders. DESIGN: A cross-sectional, clinic-based study. PARTICIPANTS: Cerebrospinal fluid samples (N=453) were obtained from healthy individuals serving as controls and from patients with Parkinson disease (PD), PD with dementia(PDD), dementia with Lewy bodies (DLB), Alzheimer disease (AD), progressive supranuclear palsy(PSP), multiple system atrophy (MSA), or corticobasal degeneration (CBD). SETTING: Neurology and memory disorder clinics. MAIN OUTCOME MEASURES: Cerebrospinal fluid biomarker levels in relation to clinical diagnosis. RESULTS: Cerebrospinal fluid levels of -synuclein were decreased in patients with PD, PDD, DLB, and MSA but increased in patients with AD. Cerebrospinal fluid levels of α-amyloid 1-42 were decreased in DLB and even further decreased in AD. Cerebrospinal fluid levels of total tau and hyperphosphorylated tau were increased in AD. Multivariate analysis revealed that these biomarkers could differentiate AD from DLB and PDD with an area under the curve of 0.90, with -synuclein and total tau contributing most to the model. Cerebrospinal fluid levels of neurofilament light chain were substantially increased in atypical parkinsonian disorders (ie, PSP, MSA,and CBD), and multivariate analysis revealed that the level of neurofilament light chain alone could differentiate PD from atypical parkinsonian disorders, with an area under the curve of 0.93. CONCLUSIONS: Ascertainment of the -synuclein level in CSF somewhat improves the differential diagnosis of AD vs DLB and PDD when combined with established AD biomarkers.The level of neurofilament light chain alone may differentiate PD from atypical parkinsonian disorders.
OBJECTIVE: To describe the clinical, electrographic, and radiographic features of status epilepticus amauroticus, or homonymous hemianopsia associated with partial status epilepticus, in 3 patients w:h subsequent resolut...OBJECTIVE: To describe the clinical, electrographic, and radiographic features of status epilepticus amauroticus, or homonymous hemianopsia associated with partial status epilepticus, in 3 patients w:h subsequent resolution of radiographic abnormalities and visual deficits. DESIGN: Case series. SETTING: Rancho Los Amigos National Rehabilitation Center in Downey, California, and the Los Angeles County + University of Southern California Medical Center. PATIENTS: One patient with a single remote seizure and 2 patients with symptomatic partial epilepsy all presented with homonymous hemianopsia. INTERVENTION: Continuous electroencephalographic monitoring, magnetic resonance imaging, and antiepileptic medical therapy for status epilepticus. MAIN OUTCOME MEASURES: Neurologic examination, electroencephalography, and magnetic resonance imaging. RESULTS: The association of homonymous hemianopsia and restricted diffusion on magnetic resonance imaging led to an initial diagnosis of ischemic infarction in 2 cases despite atypical diffusion-weighted imaging patterns. However, continuous electroencephalogram demonstrated focal epileptiform discharges in 2 cases and repetitive focal seizures in another, suggesting a diagnosis of status epilepticus amauroticus. Homonymous hemianopsia resolved in all 3 patients after escalation of the dosage of anticonvulsant therapy. Follow-up magnetic resonance imaging and electroencephalogram demonstrated complete or near-complete resolution of associated abnormalities. CONCLUSIONS: Status epilepticus amauroticus is an uncommon but important cause of homonymous hemianopsia, and it should be considered in any patient with a history of seizures, fluctuating visual symptoms, or atypical patterns of restricted diffusion involving the occipital cortex. Continuous electroencephalographic monitoring is an important diagnostic tool for the diagnosis of status epilepticus amauroticus, which may have a favorable prognosis when treated with aggressive anticonvulsant therapy.
Van Gompel JJ, Ottman R, Worrell GA
… +4 more, Marsh R, Wetjen NM, Cascino GD, Meyer FB
Arch Neurol
· 2012 Nov · PMID 22911042
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OBJECTIVE: To assess the hypothesis that use of anterior temporal lobectomy (ATL) for temporal epilepsy has diminished over time. DESIGN: Population-based cohort study. SETTING: The Rochester Epidemiology Project based i...OBJECTIVE: To assess the hypothesis that use of anterior temporal lobectomy (ATL) for temporal epilepsy has diminished over time. DESIGN: Population-based cohort study. SETTING: The Rochester Epidemiology Project based in Olmsted County, Minnesota. PARTICIPANTS: Residents of Olmsted County. MAIN OUTCOME MEASURES: Poisson regression was used to evaluate changes in ATL use over time by sex. RESULTS: Over a 17-year period, from 1993 to 2009, 847ATLs were performed with the primary indication of epilepsy(average, 50 procedures/y). Of these, 26 occurred among Olmsted County residents. The use rates declinedsignificantly between 1993 and 2000 (8 years) and 2001 and 2009 (9 years) according to Poisson regression analysis, from 1.9 to 0.7 per 100 000 person-years(P=.01). The rate of ATL use among Olmsted County residents was 1.2 (95% CI, 0.9 to 2.4) per 100 000 person years of follow-up over this 17-year period. The sex specific rates were 1.6 (95% CI, 0.9 to 2.4) and 0.7 (95%CI, 0.2 to 1.3) per 100 000 person-years for females and males, respectively. CONCLUSIONS: In this community-based cohort, the rate of ATL use was 1.2 per 100 000 person-years of followup.Use of this procedure has declined over time; the reasons for this are unknown but do not include referral pattern changes.
OBJECTIVE: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarker...OBJECTIVE: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers. DESIGN: Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months.Tract-based spatial statistics were used to assess voxel wise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum. PATIENTS: The study involved 21 patients with amyotrophic lateral sclerosis and 3 patients with primary lateral sclerosis. RESULTS: Correlation was observed between fractional anisotropy and progression rate for a region of the corticospinal tract spanning the posterior limb of the internal capsule, with a left hemisphere emphasis. Posterior limb of the internal capsule fractional anisotropy showed potential to distinguish those patients with rapid progression. Axial diffusivity significantly increased in this region in a paired t test analysis of baseline and follow-up diffusion tensor imaging, in keeping with axonal damage.No correlations were noted for the corpus callosum. CONCLUSIONS: Posterior limb of the internal capsule fractional anisotropy is a candidate prognostic marker in amyotrophic lateral sclerosis, with potential to identify incident cases with more rapid progression.
BACKGROUND: Intracranial atherosclerosis is associated with recurrent ischemic stroke. High-resolution magnetic resonance imaging can provide information about atheroma in vivo including plaque volume, composition,and ac...BACKGROUND: Intracranial atherosclerosis is associated with recurrent ischemic stroke. High-resolution magnetic resonance imaging can provide information about atheroma in vivo including plaque volume, composition,and activity. OBJECTIVE: To evaluate atherosclerosis activity of the middle cerebral artery (MCA) by high-resolution magnetic resonance imaging and determine its relationship with infarction patterns. DESIGN: Patients with MCA territory infarction or transient ischemic attack were enrolled and 3-T high resolution magnetic resonance imaging was performed in the relevant MCA. We analyzed the status of the intracranial atheroma and infarction pattern in the corresponding vascular territory. Intracranial atheroma was defined as vulnerable symptomatic plaque when it was accompanied by intraplaque heterogeneous signal intensity and plaque enhancement, and as a stable symptomatic plaque otherwise. Cerebral infarction pattern was defined as artery-to-artery embolic infarction when multiple lesions were present within the MCA territory. SETTING: A tertiary referral center. PATIENTS: A total of 34 patients were enrolled in the study;14 patients had stable symptomatic plaque, 12 had vulnerable symptomatic plaque, and 8 had no plaque (normal group). MAIN OUTCOME MEASURES: Intracranial atheroma stability and infarction pattern. RESULTS: High-resolution magnetic resonance images were acquired from 34 patients, which revealed the presence of stable symptomatic plaque in 14 patients and vulnerable symptomatic plaque in 12 patients. The patients with vulnerable symptomatic plaque more commonly demonstrated an artery-to-artery embolic infarction pattern than the patients with stable symptomatic plaque (P=.02). CONCLUSIONS: Vulnerable symptomatic plaque as determined by a high-resolution magnetic resonance imaging technique is associated with artery-to-artery embolic infarction.This novel imaging technique can provide information about intracranial atherosclerosis in vivo, which can predict the infarction pattern.
BACKGROUND: Patients with acute ischemic stroke and large artery occlusive disease (LAOD) have an increased risk for early neurologic deterioration (END) due to progressive stroke, early recurrent ischemic stroke(ERIS),...BACKGROUND: Patients with acute ischemic stroke and large artery occlusive disease (LAOD) have an increased risk for early neurologic deterioration (END) due to progressive stroke, early recurrent ischemic stroke(ERIS), or symptomatic intracranial cerebral hemorrhage(SICH). Low-molecular-weight heparin (LMWH)has been widely advocated to prevent venous thromboembolism,but its risks and benefits in early ischemic stroke are inadequately defined. OBJECTIVE: To determine the efficacy and safety of LMWH in treating END in patients with acute ischemic stroke and LAOD. DESIGN: Post hoc analysis of randomized, controlled trial. SETTING: Academic research. PATIENTS: Among 603 patients recruited, 353 patients(180 treated with LMWH, 173 with aspirin) had acute ischemic stroke and LAOD. INTERVENTIONS: Patients were randomly assigned to receive either subcutaneous LMWH or oral aspirin within 48 hours after stroke onset for 10 days, then all received aspirin once daily for 6 months. MAIN OUTCOME MEASURES: We assessed whether LMWH was superior to aspirin for the prevention of END within the first 10 days after index stroke. Early neurologic deterioration was defined as a composite end point of progressive stroke, ERIS, and SICH. RESULTS: Among 353 patients included in the study, END within the first 10 days occurred in 6.7% of LMWH allocated patients (12 of 180 patients) compared with 13.9% of aspirin-allocated patients (24 of 173). Low molecular-weight heparin was significantly associated with the reduction of END(absolute risk reduction, 7.2%; odds ratio [OR], 0.44; 95% CI, 0.21-0.92). When individual components of END were examined, LMWH was significantly associated with a lower frequency of stroke progression within the first 10 days compared with aspirin(5.0% [9 of 180] vs 12.7% [22 of 173]; OR, 0.36; 95%CI, 0.16-0.81). Meanwhile, among those taking LMWH vs aspirin, the frequency rates of ERIS were 1.1% (2 of 180) vs 0 (0); 0.6% (1 of 180) vs 1.2% (2 of 173) for SICH;and 2.2% (4 of 180) vs 2.9% (5 of 173) for symptomatic and asymptomatic cerebral hemorrhage, respectively; they showed nonsignificant trends. Early neurologic deterioration was significantly associated with 6-month disability with both LMWH(OR, 12.75; 95% CI, 3.27-49.79 on Barthel Index and OR, 18.15; 95% CI, 2.09-157.93 on modified Rankin Scale) and aspirin (OR, 6.09; 95% CI,2.44-15.20 on Barthel Index and OR, 7.50; 95% CI, 2.08-27.04 on modified Rankin Scale) groups. CONCLUSIONS: For patients with acute ischemic stroke and LAOD, treatment with LMWH within 48 hours of stroke may reduce END during the first 10 days, mainly by preventing stroke progression. The similar rate of cerebral hemorrhage between LMWH and aspirin demonstrated that LMWH may be safely used in acute ischemic stroke. TRIAL REGISTRATION: stroke center.org/trials Identifier: FISS -tris
BACKGROUND: Few data are available on the relationship between fluid-attenuated inversion recovery vascular hyperintensities and proximal middle cerebral artery occlusion prognosis. OBJECTIVES: To assess a fluid-attenuat...BACKGROUND: Few data are available on the relationship between fluid-attenuated inversion recovery vascular hyperintensities and proximal middle cerebral artery occlusion prognosis. OBJECTIVES: To assess a fluid-attenuated inversion recovery vascular hyperintensities score (FVHS) and explore its relationship with recanalization status and clinical outcomes after intravenous thrombolysis. DESIGN: Retrospective study. SETTING: Stroke unit in a university hospital. PATIENTS: Consecutive patients with proximal middle cerebral artery occlusion, thrombolysed within 6 hours, were selected from our prospective database. The FVHS (range,0-10; divided into low, medium, and high thirds) was quantified on the magnetic resonance image obtained at admission. Recanalization rates, infarction size (Alberta Stroke Program Early CT Score applied to diffusion weighted imaging [ASPECTS-DWI]), and 3-month functional outcomes (modified Rankin Scale score) were determined. Poor outcomes and large infarctions were defined as a modified Rankin Scale score higher than 2and an ASPECTS-DWI score of 5 or lower, respectively. MAIN OUTCOME MEASURES: Interaction among FVHS,recanalization status, and outcomes. RESULTS: Thirty-four patients had a low FVHS (4), 32 had a medium FVHS (5 or 6), and 39 had a high FVHS (≥7). The rate of poor functional outcome (modified Rankin Scale score >2) was higher for the group with low FVHSs than those with medium FVHSs and high FVHSs(82.3% vs 43.7% and 43.5%, respectively; P.001). Therate of 24-hour large infarctions(ASPECTS-DWI score 5)was higher for those with low FVHSs than those with medium and high FVHSs (88.2% vs 56.2% and 51.3%, respectively;P=.002). The recanalization rate was not associated with FVHS. Multivariate analysis retained low FVHS as an independent early predictor of poor clinical outcome (odds ratio=9.91; 95% CI, 2.01-48.93; P=.004)and large infarction (odds ratio=6.99; 95% CI, 1.78-27.46; P=.005).Low FVHS remained associated with poor outcomes regardless of recanalization status. Early recanalization in patients with a low FVHS decreased the poor functional outcome rate from 100% to 64.7% (P=.02). CONCLUSIONS: The FVHS is an early independent prognostic marker for patients with proximal middle cerebral artery occlusion. Synergy between FVHS and recanalization status appears to be a critical determinant of final outcomes, supporting intensive reperfusion treatment for patients with a low FVHS.
OBJECTIVE: To estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El E...OBJECTIVE: To estimate the potential diagnostic added value of the Awaji criteria for diagnosis of a myotrophiclateral sclerosis (ALS), which have been compared with the previously accepted gold standard the revised El Escorial criteria in several studies. DATA SOURCES: MEDLINE and Web of Science (until October2011). STUDY SELECTION: We searched for studies testing the diagnostic accuracy of the Awaji criteria vs the revised El Escorial criteria in patients referred with suspected ALS. DATA EXTRACTION: Evaluation and data extraction of identified studies were done independently. The Quality Assessment of Diagnostic Accuracy Studies list was used to assess study quality. We determined the proportion of patients classified as having probable/definite ALS and derived indices of diagnostic performance(sensitivity, specificity, and diagnostic odds ratio). Quantitative data synthesis was accomplished through random-effects meta-analysis, and heterogeneity was assessed with the I2 test. DATA SYNTHESIS: Eight studies were included (3 prospective and 5 retrospective) enrolling 1187 patients. Application of Awaji criteria led to a 23% (95% CI, 12% to 33%; I2=84%) increase in the proportion of patients classified as having probable/definite ALS. Diagnostic performance of the Awaji criteria was higher than the revised El Escorial criteria (pooled sensitivity: 81.1% [95%CI, 72.2% to 90.0%; I2=91%] vs 62.2% [95% CI, 49.4%to 75.1%; I2=93%]; pooled diagnostic odds ratio, 35.8[95% CI, 15.2 to 84.7; I2=3%] vs 8.7 [95% CI, 2.2 to 35.6;I2=50%]). Diagnostic accuracy of Awaji criteria was higher in bulbar- than in limb-onset cases. CONCLUSION: The Awaji criteria have a significant clinical impact allowing earlier diagnosis and clinical trial entry in ALS.
OBJECTIVE: To assess the safety, tolerability, and pharmacokinetic and pharmacodynamic effects of the -secretase inhibitor avagacestat in patients with mild to moderate Alzheimer disease (AD). DESIGN: Randomized, double-...OBJECTIVE: To assess the safety, tolerability, and pharmacokinetic and pharmacodynamic effects of the -secretase inhibitor avagacestat in patients with mild to moderate Alzheimer disease (AD). DESIGN: Randomized, double-blind, placebo-controlled,24-week phase 2 study. SETTING: Global, multicenter trial. PATIENTS: A total of 209 outpatients with mild to moderate AD were randomized into the double-blind treatment phase. The median age of the patients was 75 years,58.9% were APOE ε4 carriers, and baseline measures of disease severity were similar among groups. INTERVENTION: Avagacestat, 25, 50, 100, or 125 mg daily,or placebo administered orally daily. MAIN OUTCOME MEASURES: Safety and tolerability of avagacestat. RESULTS: Discontinuation rates for the 25-mg and 50-mg doses of avagacestat were comparable with placebo but were higher in the 100-mg and 125-mg dose groups.Trends for worsening cognition, as measured by change from baseline Alzheimer Disease Assessment Scale cognitive subscale score, were observed in the 100-mg and125-mg dose groups. Treatment-emergent serious adverse events were similar across placebo and treatment groups. The most common reason for discontinuation was adverse events, predominantly gastrointestinal anddermatologic. Other adverse events occurring more frequentlyin patients undergoing treatment included reversibleglycosuria (without associated serum glucose changes), nonmelanoma skin cancer, and asymptomaticmagnetic resonance imaging findings. Exploratory cerebrospinal fluid amyloid isoforms and tau biomarker analysis demonstrated dose-dependent but not statistically significant reductions in a small subset of patients. CONCLUSIONS: Avagacestat dosed at 25 and 50 mg daily was relatively well tolerated and had low discontinuation rates. The 100-mg and 125-mg dose arms were poorly tolerated with trends for cognitive worsening. Exploratory cerebrospinal fluid biomarker substudies provide preliminary support for -secretase target engagement,but additional studies are warranted to better characterize pharmacodynamic effects at the 25- and 50-mg doses.This study establishes an acceptable safety and tolerability dose range for future avagacestat studies in AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00810147
BACKGROUND: Increasing availability of neuroimaging has facilitated the diagnosis of cerebral sinus venous thrombosis(CSVT). However, CSVT may also present with unspecific or atypical symptoms, resulting in diagnostic de...BACKGROUND: Increasing availability of neuroimaging has facilitated the diagnosis of cerebral sinus venous thrombosis(CSVT). However, CSVT may also present with unspecific or atypical symptoms, resulting in diagnostic delay.Single reports suggested otologic symptoms as such pitfalls. OBJECTIVE: To screen patients with CSVT for otologic symptoms. DESIGN: Ten-year retrospective case series. SETTING: Primary and tertiary care university clinic. PATIENTS: Thirty-eight patients with CSVT. RESULTS: Of 38 patients with CSVT, 3 individuals hadacute unilateral hearing loss, 2 of which also had concomitant tinnitus and headache, and were initially treated at the ear, nose, and throat department. Magnetic resonance imaging after hospital discharge showed ipsilateral thrombosis of the lateral venous sinus. Two female patients took oral contraceptives, 1 of whom also had a heterozygous factor V Leiden mutation. CONCLUSIONS: Cerebral sinus venous thrombosis may present with unspecific symptoms such as acute unilateral hearing loss. If in conjunction with headache or risk factors for venous thrombosis, the suspicion of ipsilateral lateral CSVT should prompt rapid imaging including venography.