Keyhole Aqueduct Syndrome.

Keyhole aqueduct syndrome is a rare progressive neurodegenerative disorder describing a unique set of neuro-ophthalmologic, neuroimaging, and histopathological findings on autopsy. A midline mesencephalic cleft communicating with the cerebral aqueduct resembling syrinx is seen on imaging and histopathology. There are 9 cases published in the literature. We encountered a patient with vertical nystagmus, internuclear ophthalmoplegia, and progressive ataxia who has a midline cleft connecting the cerebral aqueduct with the interpeduncular cistern highlighting a distinguishing feature of this syndrome.

Longitudinal study of the substantia nigra in Parkinson disease: A high-field (1) H-MR spectroscopy imaging study.

INTRODUCTION: The value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established. METHODS: We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age-matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months. RESULTS: N-acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side-to-side difference of the ratio at baseline. By month 3, n-acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side-to-side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024). CONCLUSION: Estimation of change in the n-acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD.

Pituitary abscess presenting two years after the diagnosis of a pituitary lesion in a patient with panhypopituitarism.

Pituitary abscess is a rare condition. Here, we present the case of a young male patient who was initially found to have a pituitary lesion following the diagnosis of panhypopituitarism. Two years later, he presented with severe headache and was subsequently diagnosed intraoperatively with pituitary abscess. At a follow-up of 6 years after surgery, the patient was continuing to do very well. We discuss the differential diagnosis and demonstrate the evolution of the pituitary lesion on magnetic resonance imaging at four different time points: at the time of the detection of the initial lesion; two years later at the time of the diagnosis of the pituitary abscess; at 7 weeks post operatively; and finally after six years from the pituitary surgery.

Chronic cerebrospinal venous insufficiency and multiple sclerosis.

A chronic state of impaired venous drainage from the central nervous system, termed chronic cerebrospinal venous insufficiency (CCSVI), is claimed to be a pathologic phenomenon exclusively seen in multiple sclerosis (MS). This has invigorated the causal debate of MS and generated immense interest in the patient and scientific communities. A potential shift in the treatment paradigm of MS involving endovascular balloon angioplasty or venous stent placement has been proposed as well as conducted in small patient series. In some cases, it may have resulted in serious injury. In this Point of View, we discuss the recent investigations that led to the description of CCSVI as well as the conceptual and technical shortcomings that challenge the potential relationship of this phenomenon to MS. The need for conducting carefully designed and rigorously controlled studies to investigate CCVSI has been recognized by the scientific bodies engaged in MS research. Several scientific endeavors examining the presence of CCSVI in MS are being undertaken. At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena.

Transient shivering during Wada test provides insight into human thermoregulation.

PURPOSE: Some patients with pharmacoresistant epilepsy undergoing the Wada test experience transient shivering. The purpose of this study was to investigate various clinical and radiographic characteristics of these individuals to delineate underlying mechanisms of this phenomenon. METHODS: A systematic review of prospectively collected information on patients undergoing the Wada test was performed. All demographic, clinical, and radiographic information was obtained and reviewed by the appropriate expert in the field; statistical analysis was performed to determine the predictors of transient shivering. RESULTS: A total of 120 consecutive carotid artery injections in 59 patients were included in the study. Shivering was observed in 46% of the patients, and it was not significantly affected by gender, age, location of epileptogenic zone, brain lesion on magnetic resonance imaging (MRI), side of the first injection, duration of the hemiparesis, or excess slow wave activity on electroencephalography (EEG). However, shivering was more likely to follow sodium amobarbital injection if there was no filling of the posterior circulation on cerebral angiogram. DISCUSSION: Transient shivering during the Wada test is common. A transient but selective functional lesion of the anterior hypothalamus produced by the effects of sodium amobarbital may result in disinhibition of the posterior hypothalamus and other brainstem thermoregulatory centers, thereby inducing transient shivering.

Acute transverse myelitis with normal brain MRI : long-term risk of MS.

OBJECTIVE: To investigate the long-term risk of developing MS in patients presenting with acute transverse myelitis (ATM) and normal brain MRI scans at onset. METHODS: We studied 58 ATM patients with normal brain MRI at presentation for up to 5 years with serial neurologic and imaging studies. All patients underwent CSF analysis at onset which was defined positive if two or more IgG oligoclonal bands and/or elevated IgG index were present. Brain and spinal cord MRI scans were obtained every 6 months for the first 2 years, and annually thereafter unless the patient experienced a second neurologic attack different from the initial episode to confirm CDMS or there was demonstration of MRI lesions confirming dissemination in time and space to fulfill McDonald imaging criteria to diagnose MS. RESULTS: Seventeen of 58 (29%) patients developed MS of which 7 (41%) patients developed CDMS and 10 (59%) developed MS using McDonald Imaging Criteria. Mean time to CDMS by a second clinical attack was 11. 1 months compared to 19. 2 months by MRI lesions (P = 0. 03). None of the patients developed MS after 24 months of onset. All 17 patients who developed MS had positive CSF although 15 patients who had positive CSF did not develop MS during the 5 years of follow-up. CONCLUSIONS: The majority of patients with ATM and normal brain MRI do not develop MS after 5 years of follow-up confirming the relatively low risk compared to patients with abnormal brain MRI scans. CSF is helpful in distinguishing patients more likely to develop MS. Compared to clinical attacks, serial imaging may not lead to an earlier diagnosis in ATM patients with normal brain MRI.

Fulminant Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is increasingly being recognized as a diagnosis in patients presenting with thunderclap headaches. In the vast majority of the cases, the syndrome follows a benign course and patients recover completely without any significant therapeutic intervention. In the rarest of cases, RCVS follows a monophasic course with rapid worsening, severe neurological deficits, and poor outcomes. We present the case of a 25-year-old female who presented with headaches which were worsening over 1 week. She was admitted to the hospital and rapidly worsened to develop severe neurological deficits over the next day. Initial computed tomography scan showed areas of hemorrhage and multiple ischemic strokes. Computed tomography angiogram and a conventional cerebral angiogram both revealed multifocal vasoconstriction, highly suggestive of RCVS. Despite aggressive medical and surgical management, the patient continued to worsen and eventually died. Autopsy findings did not show evidence of vasculopathy or any other underlying disorder, further supporting the diagnosis of RCVS. The RCVS is usually a benign self-remitting condition which commonly affects young females and presents with an insidious onset of headaches. Rarely, it can have a fulminant course with devastating outcomes. This case illustrates an exceptionally uncommon clinical course of RCVS and the challenges in its treatment.

Imaging of neurologic disorders associated with pregnancy and the postpartum period.

Diverse pathologic conditions affect the central nervous system (CNS) and pituitary gland during pregnancy and the puerperium. Some are specific to the physiologic process of reproduction (eg, eclampsia, postpartum cerebral angiopathy, Sheehan syndrome, lymphocytic adenohypophysitis). Others are nonspecific but occur more often in pregnant women (eg, cerebral infarction, dural venous thrombosis, pituitary apoplexy). Recognition of the characteristic imaging findings in eclampsia, for example, may allow exclusion of other disorders. Even when imaging changes are nonspecific, knowledge of those entities associated with pregnancy and awareness of the increased likelihood of certain diseases in pregnancy will allow a more informed differential diagnosis. Differentiation of primary nonaneurysmal subarachnoid hemorrhage (SAH) from aneurysmal SAH is an example. Moreover, earlier use of imaging will result in fewer delayed diagnoses. For example, magnetic resonance venography allows early diagnosis of cerebral venous thrombosis. Even when the imaging changes are less specific, knowledge of likely possibilities will lead to more appropriate earlier use of imaging. For example, the stimulatory effects of pregnancy on prolactinoma, meningioma, hemangioblastoma, vestibular schwannoma, and metastatic tumors such as breast cancer and choriocarcinoma suggest the early use of CNS imaging to avoid the consequences of a delayed diagnosis.

Leptomeningeal metastasis in a patient with squamous cell carcinoma of the uterine cervix: Report of a case and review of the literature.

Leptomeningeal spread of advanced squamous cell carcinoma (SCC) of the uterine cervix is unusual. To our knowledge, very few cases were reported in the English literature. We report a case of a 39-yr-old woman who presented with leptomeningeal metastasis from a stage IIb SCC of uterine cervix. The diagnosis was made by cytomorphological examination of smears obtained from cerebrospinal fluid. The cytomorphological features are demonstrated.

The Relationship Between Brain MR Spectroscopy and Disability in Multiple Sclerosis: 20-Year Data from the U.S. Glatiramer Acetate Extension Study.

BACKGROUND AND PURPOSE: Conventional MRI techniques do not necessarily provide information about multiple sclerosis (MS) disease pathology or progression. Nonconventional MRI techniques, including proton magnetic resonance spectroscopy (1 H-MRS), are increasingly used to improve the qualitative and quantitative specificity of MR images. This study explores potential correlations between MRI measures of disease and disability progression as measured by the Expanded Disability Status Scale (EDSS), Functional Systems (FS), and ambulation index scores in a unique cohort of MS patients treated with glatiramer acetate that has been closely monitored for over 20 years. METHODS: This was a multicenter, open-label, cross-sectional MRI substudy among participants in the GA-9004 open-label extension of the 36-month, double-blind GA-9001 study, timed to coincide with the prospectively planned 20-year clinical exam. RESULTS: Of 64 patients who participated in the MRI substudy, results are presented for the 39 patients (61%) who had a 1 H-MRS assessment at 20 years of treatment. Both total N-acetylaspartate relative to total creatinine (tNAA/tCr) concentration ratio and T1 lesion volume were found to be robustly associated with disability levels with different statistical approaches. Gray matter (GM) volume was found to be a more consistent parameter than white matter (WM) volume for disability allocation. The elastic net algorithm showed a trade-off between WM and GM volumes for disability estimation when different disability definitions were used. CONCLUSIONS: Among patients with MS receiving long-term glatiramer acetate therapy, consistent effects on disability levels indicated by EDSS and pyramidal FS score thresholds were found for tNAA/tCr concentration ratio and T1 lesion volume.

Cerebral Gray Matter Atrophy Is Associated with the CSF IgG index in African American with Multiple Sclerosis.

BACKGROUND AND PURPOSE: African American (AA) patients with multiple sclerosis (MS) have been reported to have a more aggressive disease course compared to their white counterparts. We explored the relation of gray matter (GM) volume, a marker of tissue injury, and cerebrospinal fluid (CSF) IgG index in both AA and white MS patients. METHODS: This was a cross-sectional study of 150 self-identified AA and 150 white patients with MS who underwent magnetic resonance imaging scan of brain and CSF sampling. Intrathecal IgG synthesis was quantified as IgG index. The Spearman test was used for univariate correlation analysis, followed by generalized linear model (GLM) to assess the effect of race on the correlation between IgG index and GM volume. RESULTS: The GM volume was inversely related to the IgG index for the entire group (rho = -.57, P < .0004). The AA group showed a stronger correlation (rho = -.893, P < .00004), as compared to whites (rho = -.019, P = .85), between GM and IgG index. Furthermore, GLM analysis showed a significant effect of race on the relation between IgG index and GM volume (P < .0005). CONCLUSIONS: AA patients with MS have lower GM volume and a stronger inverse correlation between GM volume and CSF IgG index, compared to the whites. These findings suggest a potentially prominent role of humoral immunity in mediating tissue injury in AA patients with MS.

Spinal cord atrophy in multiple sclerosis and relationship with disability across clinical phenotypes.

BACKGROUND: Several studies have shown a relationship between spinal cord atrophy and clinical disability in patients with multiple sclerosis (MS). OBJECTIVES: We examined the correlation between cervical cord cross-sectional area at the C2 vertebral level (CSA-C2) and the expanded disability status scale (EDSS) in patients with relapsing-remitting and progressive forms of MS. The latter included both secondary and primary progressive MS patients. METHODS: A total of 150 patients with MS were recruited from the Wayne State University MS clinic. Ninety-three had relapsing-remitting MS and 57 patients had progressive MS. MRI scan of the cervical cord was obtained for each patient. Correlation studies and multivariate regression analysis was performed, blinded to clinical status. RESULTS: The mean age was 41.3 year old, 64.6% were women, mean disease duration was 11.2 years, CSA-C2 was 80.2mm(2) and mean EDSS was 3.8. There was significant correlation between CSA-C2 and EDSS (r -0.75, p<0.0001). Sub-group analysis showed CSA-C2 was 68.6mm(2) and 87.3mm(2) in the progressive and relapsing-remitting groups, respectively (p<0.0001). Multivariable regression showed that CSA-C2 was a significant predictor of disability independent of disease duration, and phenotype. CONCLUSIONS: Our study demonstrates that CSA-C2 has a strong correlation with clinical disability in both RRMS and progressive MS. Greater spinal cord atrophy was seen in patients with progressive than relapsing-remitting MS. CSA-C2, disease duration, and phenotype are independent predictors of disability.

Diaphragmatic and crural FDG uptake in hyperventilating patients: a rare pattern important to recognize.

The authors describe various patterns of F-18 fluorodeoxyglucose (FDG) accumulation in the diaphragm and crura. They present 6 patients in whom incidental diaphragmatic and crural uptake of FDG was observed during positron emission tomography (PET). Hyperventilation is thought to be the potential underlying mechanism of this condition.

Retroperitoneal malignant peripheral nerve sheath tumor: evaluation with serial FDG-PET.

Retroperitoneal malignant peripheral nerve sheath tumor (MPNST), a rare type of neurogenic tumor, was diagnosed in a 14-year-old girl with a history of neurofibromatosis type 1 (NF1). Immunochemistry demonstrated spindle cells positive for S-100 protein. The patient had multiple tumor recurrences and she was evaluated with serial F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). A tumor in the right iliac wing showed increased FDG uptake on PET. FDG-PET played an important role in therapy planning and subsequent follow up. This case emphasizes the important role FDG-PET could play in the staging, restaging, and posttherapy follow up of MPNST.

Fatal encephalitis due to BK virus in a patient with common variable immunodeficiency: a case report.

Encephalitis due to BK virus is a rare condition. Here, we describe a young male patient with common variable immunodeficiency who developed fatal encephalitis due to BK virus. The patient presented initially with ocular symptoms that were followed by behavioral changes and spastic quadriparesis. Diagnosis was made by the compatible clinical findings and detection of viral DNA by polymerase chain reaction in the cerebrospinal fluid. To the best of our knowledge, this is the first report of BK virus encephalitis in a patient with common variable immunodeficiency. We suggest that BK virus should be suspected in cases of encephalitis; particularly in patients with immunodeficiency.

Effect of disease-modifying therapies on brain volume in relapsing-remitting multiple sclerosis: results of a five-year brain MRI study.

OBJECTIVE: To compare the long-term effect of disease-modifying therapies (DMT) on brain volume loss in relapsing-remitting MS (RRMS) patients. METHODS: We conducted a study to examine the effect of daily glatiramer acetate (GA), weekly low dose interferon beta (LD-IFNB), and high-dose high-frequency interferon beta disease (HD-IFNB) on brain volume loss over 5 years in RRMS patients. All patients were previously treatment naïve, had disease duration ≤5 years at the time of initiating DMT, and subsequently received the same DMT for 5 years continuously. The percentage change in brain volume (PCBV) was measured using fully automated software. MRI analysis was performed blinded to treatment allocation. RESULTS: The adjusted PCBV from baseline to year 5 was -2.27% in GA, -2.62% in LD-IFNB, and -3.21% in the HD-IFNB groups (-2.27 vs -2.62, p=0.0036; -2.27 vs -3.21, p<0.0001; -2.62 vs -3.21, p<0.0001). These data remained unchanged from year 1 to year 5, after adjusting for pseudoatrophy in the first year. A group of RRMS patients that remained untreated for a period ranging from 8 to 24 months, served as controls. All treatment groups were significantly better than the rate of projected brain volume loss in the untreated group over 5 years (p<0.0001). CONCLUSIONS: Global brain volume loss is a dynamic process even in relatively early RRMS patients that occurs despite intervention with therapy. However, all DMT significantly reduced the loss of brain volume compared to no treatment. The GA-treated group experienced the least reduction in brain volume over 5 years, compared to the LD-IFNB and HD-IFNB treated groups. These differences could be partly related to the immunologic consequences of GA therapy in RRMS.

Anterior horn cell loss from subdural hygroma: a consequence of spontaneous spinal fluid leak.

We describe a case of a 50-year-old man with bilateral shoulder girdle weakness caused by anterior subdural hygroma secondary to a previous spontaneous CSF leak. The CSF leak occurred and resolved 16 years prior to presenting with a 6-year progressive painless, asymmetric proximal muscle weakness involving both upper extremities. Current examination reveals remarkably restricted atrophy and weakness in bilateral C5-6 muscles and absent biceps and brachioradialis reflexes. Neuroimaging shows a subdural CSF collection extending from C1 to L2 anteriorly causing thecal sac effacement at the C4 level and secondary Chiari deformity. The clinical picture demonstrates severe weakness in C5-6 muscles with sparing of all other myotomes. The acute clinical features as well as neuroimaging characteristics of spontaneous CSF leak are well known but the late effects are less described. The development of a subdural fluid collection secondary to a spinal fluid leak can cause damage to the anterior spinal cord years after the leak. The underlying pathophysiology of the motor neuron loss remains unclear but there appears to be a pressure effect localized to the C4-5 region. The possibility that intervention to prevent or treat the subdural CSF collection might have avoided the shoulder girdle weakness is considered.

Mondini malformation associated with diastematomyelia and presenting with recurrent meningitis.

The authors report the case of 5-year-old girl who presented with 4 episodes of recurrent meningitis. Her initial workup revealed a lumbosacral dermoid sinus associated with diastematomyelia and a tethered cord. Therefore, a surgical repair to correct the anomaly was performed. However, another episode of meningitis occurred after surgery, and a subsequent temporal bone scan revealed the presence of left Mondini dysplasia. To the authors' knowledge, this is the first report of Mondini dysplasia in association with diastematomyelia.