Disproportionately Large Communicating Fourth Ventricle: Pearls for Diagnosis and Management.

Introduction Disproportionately large communicating fourth ventricle (DLCFV) is an unusual presentation of communicating hydrocephalus, in which patients with hydrocephalus have a disproportionately enlarged fourth ventricle in the absence of obstructive pathology. We present six cases of DLCFV which, to date, is the largest series of this relatively rare condition. We highlight the significance of diagnosis and its differentiation from trapped fourth ventricle (TFV) and discuss the nuances for optimal management of DLCFV. Methods Retrospective case series of consecutive patients with DLCFV, managed by the senior author (LT) over a 10-year period. Results Six cases were identified, five of whom had previous posterior fossa surgery and one with previous encephalitis. All patients presented with cerebellar signs, the initial group had unsuccessful initial management with typical cerebrospinal fluid (CSF) diversion. Consistent symptom resolution was achieved by the application of negative CSF pressures via external ventricular drainage (EVD), maintained with subsequent ventriculopleural shunt (VPL), valveless lumbopleural shunt (LPS) or valveless ventriculoperitoneal shunt (VPS), or proceeding directly to a low-pressure system. Conclusions DLCFV is a diagnosis characterised by cerebellar dysfunction, with or without cranial nerve palsies, often in the setting of previous posterior fossa pathology. Optimal management relies on knowledge of this unique diagnostic entity, and use of an EVD at negative pressures to confirm symptomatic and radiological improvement prior to definitive treatment.

The role of ICP monitoring in patients with persistent cerebrospinal fluid leak following spinal surgery: a case series.

BACKGROUND: Cerebrospinal fluid (CSF) leak following spinal surgery is a relatively common surgical complication. A disturbance in the underlying CSF dynamics could be the causative factor in a small group of patients with refractory CSF leaks that require multiple surgical repairs and prolonged hospital admission. METHODS: A retrospective case series of patients with persistent post spinal surgery CSF leak referred to the hydrocephalus service for continuous intracranial pressure (ICP) monitoring. Patients' notes were reviewed for medical history, ICP data, radiological data, and subsequent management and outcome. RESULTS: Five patients (two males/three females, mean age, 35.4 years) were referred for ICP monitoring over a 12-month period. These patients had prolonged CSF leak despite multiple repair attempts 252 ± 454 days (mean ± SD). On ICP monitoring, all five patients had abnormal results, with the mean ICP 8.95 ± 4.41 mmHg. Four had abnormal pulse amplitudes, mean 6.15 mmHg ± 1.22 mmHg. All five patients underwent an intervention. Three patients underwent insertion of ventriculoperitoneal (VP) shunts. One patient had venous sinus stent insertion and one patient underwent medical management with acetazolamide. All five of the patients' CSF leak resolved post intervention. The mean time to resolution of CSF leak post intervention was 10.8  ± 12.9 days. CONCLUSIONS: Abnormal cerebrospinal fluid dynamics could be the underlying factor in patients with a persistent and treatment-refractory CSF leak post spinal surgery. Treatments aimed at lowering ICP may be beneficial in this group of patients. Whether abnormal pressure and dynamics represent a pre-existing abnormality or is induced by spinal surgery should be a subject of further study.

Active and silent thyroid-stimulating hormone-expressing pituitary adenomas: presenting symptoms, treatment, outcomes, and recurrence.

OBJECTIVE: Thyroid-stimulating hormone (TSH)-expressing pituitary adenomas are a rare but important entity with a spectrum of clinical manifestations. There are currently no data to indicate whether a difference exists in the natural progression of active and silent TSH-expressing pituitary adenomas (defined by the presence or absence of clinical hyperthyroidism, respectively). Here we report our experience (including presenting symptoms, treatment, and outcome) with managing both groups over 11 years in the largest single-center study published to date. METHODS: We reviewed retrospectively all patients with histopathologically proven TSH-expressing pituitary adenomas who presented to our center between 2002 and 2012. Data reviewed included clinical presentation, biochemical status, tumor size, management, histopathologic results, and long-term postoperative outcomes. RESULTS: A total of 32 patients (16 male) were identified from a total of 902 operations for pituitary adenomas performed between 2002 and 2012. Mean follow-up was 6.7 years. One-quarter (25%) of patients were clinically hyperthyroid at presentation. Visual disturbance was the commonest presenting complaint in 34%. All patients underwent transsphenoidal surgery. Thirty-one percent of patients had a recurrence. The clinically active and silent TSH-expressing pituitary adenomas behaved in a similar manner with respect to recurrence rates. CONCLUSIONS: TSH-expressing pituitary adenomas present with a wide clinical spectrum. Visual disturbances are common. Despite radiologic evidence of clearance after surgery and extended follow-up, they may still recur whether clinically "active" or "silent." Our data support the need for close, long-term follow-up of these patients.

An unusual anatomic and geographic location of primary germinoma of the fourth ventricle.

Intracranial germinoma is most commonly found in the pineal and suprasellar regions. The medulla oblongata and fourth ventricle are rare sites of primary germinoma, with only 12 previous patients reported, all from the Far East. To our knowledge, we report the first patient from Europe. A 25-year-old female of Afro-Caribbean origin presented with several weeks of worsening migraines, dizziness, tachycardia and veering to the right whilst walking. MRI revealed a lesion in the fourth ventricle, which was treated with surgical debulking and post operative radiotherapy. Two months following completion of radiotherapy, MRI showed almost complete resolution of the enhancing disease within the primary tumour area and no intraspinal pathological enhancement. This patient highlights the importance of considering germinoma in the differential diagnosis of all medullary masses with extension into the fourth ventricle irrespective of geographic location.

Pseudotumor cerebri presenting with visual failure in promyelocytic leukemia: a case report.

INTRODUCTION: Pseudotumor cerebri secondary to all-trans retinoic acid in acute promyelocytic leukemia is a reported but rare complication of the therapy. Most cases improve following the discontinuation of all-trans retinoic acid. There is no published literature on how to manage such patients if severe symptoms of increased intracranial pressure continue after discontinuation of the drug. CASE PRESENTATION: We report the case of a 16-year-old Afro-Caribbean woman with aggressive secondary pseudotumor cerebri who presented to our facility with visual failure that persisted despite discontinuation of all-trans retinoic acid. A lumbar drain was inserted for 11 days resulting in symptomatic relief of headaches and objective improvement of visual failure. Pressure settings were titrated regularly to ensure optimal symptomatic relief. CONCLUSIONS: The use of a lumbar drain for continuous drainage of cerebrospinal fluid in patients with all-trans retinoic acid-induced pseudotumor cerebri resistant to all-trans retinoic acid discontinuation is a feasible management option. This method can be used when other less invasive measures have failed to improve signs and symptoms. Permanent drainage of cerebrospinal fluid with a shunt may also provide a long-term viable management strategy but the use of a lumbar drain may be preferable if the cause of pseudotumor cerebri is known to be self-limiting.

An open-label extension trial of risperidone monotherapy in the treatment of bipolar I disorder.

The primary objective of this 9-week open-label extension trial was to assess the effects of risperidone monotherapy in patients with acute bipolar I disorder who completed treatment in two preceding 3-week double-blind trials. Patients with DSM-IV bipolar I disorder, experiencing an acute manic episode, received a flexible dose of risperidone (1-6 mg/day) or placebo in two independent double-blind, randomized, 3-week monotherapy trials. Completers who required ongoing treatment were eligible to enter this open-label 9-week extension trial during which all patients received risperidone. The primary efficacy measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary efficacy measures included the Clinical Global Impressions-Severity Scale, Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale and Global Assessment Scale. Safety assessments included adverse event reports, laboratory tests, and the Extrapyramidal Symptom Rating Scale (ESRS). Of the 283 patients who entered the extension study, 160 had previously received risperidone (RIS/RIS) in the acute treatment trial and 123 had received placebo (PLA/RIS). This study was completed by 71% of these patients. The mean+/-SE modal dose of risperidone was 4.6+/-1.5 mg/day. Patients in both the RIS/RIS and PLA/RIS groups improved significantly at the endpoint of the 9-week open-label study compared to their open-label baseline scores (-5.2+/-0.69, P<0.001 and -9.12+/-1.44, P<0.001, respectively) on the YMRS. Furthermore, changes from double-blind baseline to open-label endpoint were -29.4+/-1.0 in the RIS/RIS group and -23.9+/-1.4 in the PLA/RIS group. Significant improvements from both double-blind and open-label baseline were seen at week 1 of the open-label trial (P<0.001) and at each subsequent timepoint. A similar pattern was observed on the secondary measures of efficacy. Most frequent adverse events were extrapyramidal disorder (18%) and somnolence (12%). Most adverse events were mild or moderate in severity. The mean score for the Parkinsonism subscale of the ESRS was 1.1 at open-label baseline, and decreased by 0.1 at endpoint. Mean increase in body weight from open-label baseline was 0.6 kg in patients treated with placebo in the preceding double-blind trial and 1.2 kg in patients previously treated with risperidone. Risperidone treatment was well tolerated and resulted in further improvement during the 9-week extension, beyond the 3 weeks of acute treatment. Patients switched from placebo to risperidone improved markedly. Risperidone treatment did not induce depression.

Role of nondiagnostic exercise-induced ST-segment abnormalities in predicting future coronary events in asymptomatic volunteers.

BACKGROUND: Whether exercise-induced ST-segment depression <1 mm is an independent predictor of future coronary events (CEs) in asymptomatic subjects is unknown. METHODS AND RESULTS: We performed maximal treadmill exercise tests on 1083 volunteers from the Baltimore Longitudinal Study of Aging who were free from clinical coronary heart disease. Exercise ST-segment changes were stratified by Minnesota code criteria: 11:1 (n=213), flat or downsloping ST depression > or =1 mm; 11:2 (n=66), flat or downsloping ST depression > or =0.5 mm and <1 mm; 11:4 (n=124), ST-J depression > or =1 mm with slowly rising ST segments; and 11:5 (n=69), minor ST depression (<0.5 mm) before exercise that worsened to flat or downsloping ST depression > or =1 mm during or after exercise. Risk of CE was compared with subjects with normal exercise ECG (n=611). Over a mean follow-up of 7.9 years, 76 subjects developed CEs (angina pectoris, myocardial infarction, or coronary death). On univariate analysis, age (relative risk [RR]=1.07/year, P<0.0001), male sex (RR=1.98, P=0.009), plasma cholesterol (RR=1.02/mg per dL, P<0.0001), hypertension (RR=2.23, P=0.002), duration of exercise (RR=0.71/min, P=0.0001), and systolic blood pressure at peak effort (RR=1.02/mm Hg, P=0.002) were associated with CE. By Cox proportional hazards analysis, age (RR=1.06/year, P<0.0001), male sex (RR=2.76, P=0.0002), plasma cholesterol (RR=1.02 per 1 mg/dL, P<0.0001), duration of exercise (RR=0.87/min, P=0.004), and ST-segment changes coded as either 11:1 (RR=2.70, P=0.0005) or 11:5 (RR=2.73, P=0.04) were independent predictors of CE. CONCLUSIONS: Both a classic ischemic ST-segment exercise response and intensification of minor preexercise ST-segment depression to levels > or =1 mm independently predicted future CE in this asymptomatic population. Neither slowly rising ST depression nor horizontal ST depression <1 mm was prognostic.