Christopher Stephen

Complicated spontaneous intracranial hypotension treated with intrathecal saline infusion

Spontaneous intracranial hypotension typically results from a spontaneous cerebrospinal fluid (CSF) leak.1 ,2 Symptoms include orthostatic headache and meningism without a recent dural puncture,2 and may be associated with distant and trivial trauma.3 The diagnosis may be made clinically by the typical headache and supported by pachymeningeal enhancement on MR scan or a low CSF pressure at lumbar puncture.2 If severe and continued, the low pressure can have serious complications, including brain sagging with subdural hygromas,4 cerebral venous sinus thrombosis,5 subdural haematoma2 and subarachnoid haemorrhage.6 Indicators of a serious complication include cranial nerve palsy and worsening mental status, progressing to coma.4 Herniation can result from a pressure differential, with spinal intrathecal pressure lower than intracranial pressure. Left untreated, this can result in significant morbidity or death. Treatment may be conservative, involving strict bed rest, use of the Trendelenburg position, intravenous/oral hydration and caffeine. If these measures fail, an epidural blood patch, starting ‘blindly’ in the lumbar region, may help.7 People with persistent symptoms need imaging with a radionuclide scan or CT/MR myelography to help localise the CSF leak, followed by a targeted epidural blood patch or surgical repair.3 ,7 Intrathecal saline infusion has succeeded in treating otherwise refractory spontaneous intracranial hypotension.8–12 We report a case of spontaneous intracranial hypotension complicated by bilateral subdural hygromas and subdural haematomas, with uncal herniation, coma and bilateral posterior cerebral artery infarctions. We treated her with an intrathecal saline infusion under pressure monitoring, with rapid resolution of coma. A 57-year-old woman presented to another hospital with orthostatic headache, neck pain, nausea and vomiting. The previous day, she had coughed vigorously during a viral illness. She re-presented 1 week later with persistent symptoms; examination was normal, but a CT scan of the head …

Functional neurological disorders in Parkinson disease

Objective To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. Methods A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. Results Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). Conclusions A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.

Neuropsychiatric Factors Linked to Adherence and Short-Term Outcome in a U.S. Functional Neurological Disorders Clinic: A Retrospective Cohort Study

Despite advancements in the assessment and management of functional neurological disorder (FND), the feasibility of implementing a new standard of care remains unclear. Chart reviews were performed for 100 patients with motor FND to investigate factors related to treatment adherence and clinical improvement over an average follow-up of 7 months. Of 81 patients who returned for follow-up, a history of chronic pain disorder inversely correlated with improvement. Of the 50 individuals newly referred for treatment, adherence correlated with improvement, while having abnormal neuroimaging inversely correlated with improvement. This study supports the feasibility of applying a new standard of care for FND.

Mutations in TGM6 induce the unfolded protein response in SCA35

Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations in TG6 induce cerebellar degeneration by an unknown mechanism. We identified seven patients bearing new mutations in TGM6. To gain insights into the molecular basis of mutant TG6-induced neurotoxicity, we analyzed all the seven new TG6 mutants and the five TG6 mutants previously linked to SCA35. We found that the wild-type (TG6-WT) protein mainly localized to the nucleus and perinuclear area, whereas five TG6 mutations showed nuclear depletion, increased accumulation in the perinuclear area, insolubility and loss of enzymatic function. Aberrant accumulation of these TG6 mutants in the perinuclear area led to activation of the unfolded protein response (UPR), suggesting that specific TG6 mutants elicit an endoplasmic reticulum stress response. Mutations associated with activation of the UPR caused death of primary neurons and reduced the survival of novel Drosophila melanogaster models of SCA35. These results indicate that mutations differently impacting on TG6 function cause neuronal dysfunction and death through diverse mechanisms and highlight the UPR as a potential therapeutic target for patient treatment.

Clinical case conference: A 41‐year‐old woman with progressive weakness and sensory loss

Case Presentation (Dr. Christopher D. Stephen) A 41-year-old right-handed woman was brought by her friend to the Emergency Department with a severalmonth history of progressive upper and lower extremity weakness and sensory changes, resulting in her being unable to walk or care for herself. The patient had a history of chronic low back pain, and a distant history of abuse of prescribed opiate analgesics for this problem, resulting in methadone maintenance. She had been unemployed and homeless, living with a friend, but otherwise she had been well until the past 4 months, when symptoms started with the gradual onset of the sensation of her feet and hands falling asleep. She tried to rub or shake out the paresthesias. When this failed, she saw a neurologist, who performed an electromyogram and nerve conduction studies 2 months prior to admission. She was told that her symptoms and testing were consistent with carpal tunnel syndrome and that she should see an orthopedic surgeon, but she did not act on the recommendation. She subsequently developed progressive weakness and stiffness in her hands. When she was showering, she noted difficulty getting into the shower and holding the shampoo, and when she closed her eyes, she lost balance. She also noted that when she put her chin to her chest she developed a shooting, vibrating pain down her spine. She then developed a vibrating pain from the knees descending to the ankles, which her primary care physician treated with gabapentin 400mg 3 times daily. Her symptoms slowly worsened, and the weakness in her hands progressed from difficulty picking up objects, to being unable to hold a pen to sign her name, and eventually to having almost no use of her hands. Her fingers would curl up and she could not straighten them out. Her legs then became stiff, making her walking unsteady, with poor balance. She complained of worsening sensation in her hands and feet, which was eventually so poor that she could not feel items when placed in her hand and could not appreciate hot or cold with the soles of her feet. One week before admission she stubbed her toes on the floor, but was unaware that this caused injury until she noticed that the tips of her toes were bleeding. She denied urinary or bowel symptoms. She also noted cognitive slowing over the past few months. She denied any recent illness, trauma, or other inciting factors related to these events. The friend whom she lived with found it progressively more difficult to care for her, and took her to the emergency department, where she was admitted. The patient had a history of hypertension, as well as lumbar disk disease treated with surgery 15 years earlier. She had chronic back pain, treated with methadone. She had had a Roux-en-Y procedure for obesity 4 years earlier. She was edentulous and wore dentures that did not fit well, requiring daily application of denture adhesive to hold them in place. Medications included metoprolol succinate, azilsartan, medroxyprogesterone acetate, clonazepam, zolpidem,

Tracheobronchial amyloidosis in a patient with Sjogren syndrome.

Pulmonary amyloidosis in the setting of Sjogren syndrome is rare. It most commonly presents in form of multinodular disease with or without cysts formation. Amyloid plaques may also deposit in the airway submucosa, causing airway narrowing; the condition referred as “tracheobronchial amyloidosis” (TBA). Patients with this condition most commonly present with postobstructive pneumonia, wheezing, and occasionally hemoptysis. Endoscopic therapies, using flexible forceps with or without laser therapy is crucial to alleviate the obstruction and control the bleeding. Other therapeutic modalities such as external beam radiation has been shown to be promising; however, further data are still needed. To our knowledge, our patient is the first reported case of TBA in a setting of Sjogren syndrome.

Electrocardiogram Abnormalities Suggest Aberrant Cardiac Conduction in Huntington's Disease: ECG Abnormalities in Huntington's Disease

There is increasing evidence that the effects of Huntingtons disease (HD) extend beyond the central nervous system. In particular, significant cardiac dysfunction has been described in transgenic mouse models and suggested in symptomatic patients, in whom cardiac involvement could provide an independent risk for sudden cardiac death.

Non-motor features of Parkinson’s disease in a nested case–control study of US men

Background Several non-motor features may individually contribute to identify prodromal Parkinson’s disease (PD), but little is known on how they interact. Methods We conducted a case–control study nested within the Health Professionals Follow-up Study in a large cohort of men age 40–75 at recruitment in 1986. Cases (n=120) had confirmed PD, were<85 in January 2012, returned a 2012 questionnaire with questions on probable rapid eye movement sleep behaviour disorder (RBD) and constipation sent to all cohort participants and completed in 2014 the Brief Smell Identification Test and a questionnaire assessing parkinsonism and other non-motor PD features (including depressive symptoms, excessive daytime sleepiness, impaired colour vision and body pain). Controls (n=6479) met the same criteria as cases, except for the PD diagnosis. Results Concurrent constipation, probable RBD and hyposmia were present in 29.3% of cases and 1.1% of controls, yielding an age-adjusted OR of 160(95%CI 72.8to353) for three features versus none. The odds of PD increased exponentially with additional non-motor features (OR for 6–7 features versus none: 1325; 95%CI333to5279). Among men without PD, the number of non-motor features was associated with odds of parkinsonism (OR for 6–7 features versus none: 89; 95%CI21.2to375). We estimated that in a population with a prodromal PD prevalence of 2%, concurrent constipation, probable RBD and hyposmia would have a maximum sensitivity of 29% and a positive predictive value (PPV) of 35%. The PPV could increase up to 70% by including additional features, but with sharply decreased sensitivity. Conclusions Concurrent constipation, probable RBD and hyposmia are strongly associated with PD. Because these features often precede motor symptoms and their co-occurrence could provide an efficient method for early PD identification.

Disparities in epilepsy surgery in the United States of America

The aim is to describe the epidemiology of epilepsy surgery in children and adults in the United States. We performed a descriptive study of the National Inpatient Sample (NIS) for the year 2012 and the Kids’ Inpatient Database (KID) for the period 2010–2012, the largest all-payer databases on inpatient data in the USA. These databases estimate 97% of all inpatient hospital discharges in the USA. In the KID, 12,899 (0.2%) of admission records had brain surgery and 600 of the 4900 (12.2%) admissions with focal refractory epilepsy underwent epilepsy surgery. Epilepsy surgery occurred in 60% of Whites, 7% of Blacks, 15% of Hispanics, and 10% of other races. In the NIS, 99,650 (0.3%) of admission records had brain surgery and 1170 of the 9775 (12%) admissions with focal refractory epilepsy underwent epilepsy surgery. Epilepsy surgery occurred in 69% of Whites, 7% of Blacks, 9% of Hispanics, and 8% of other races. In both the KID and the NIS, lower socioeconomic status was mildly underrepresented in epilepsy surgery. In both pediatric and adult admissions, there was an overrepresentation of Whites and underrepresentation of Blacks, which persisted after stratifying by socioeconomic status. Females were underrepresented in epilepsy surgery, but gender disparities were partially explained by differences in socioeconomic status. Epilepsy surgery is not equally distributed across races in the USA and these differences are not fully attributable to differences in socioeconomic status. Racial disparities in epilepsy surgery similarly affect children and adults.

A Case of Functional Dystonia with Associated Functional Neurological Symptoms: Diagnostic and Therapeutic Challenges

History of Present Illness Mrs. M is a 41-year-old, married, right-handed Caucasian female on leave fromwork, with a history of depression, anxiety, and childhood physical and emotional abuse, who was referred to a specialized dystonia clinic for a second opinion regarding possible dystonia, hand and head tremors, slowed movements, and memory trouble. RegardingMrs.M’s neurological history, as a teenager she had two unexplained seizure-like events with normal interictal EEGs, which resolved spontaneously without treatment. She also reported a minor head injury as a child, without loss of consciousness, after falling out of a moving vehicle. Approximately eight months prior to her presentation in August 2015, she noticed paroxysmal abnormal movements. She initially reported “finger tapping” movements in her hands that she described as “tics” and that would last for a few minutes and completely resolve. She recalled that in the setting of a stressful prior job, working with brain injury patients, she had an episode of unexplained loss of consciousness one month prior to initial symptom onset. Later, she developed brief hand-shaking episodes, and occasionally both legs would tremble after jogging or other exercise. She