Stefan Weiler

Disease-specific sparing of the anterior semicircular canals in bilateral vestibulopathy

OBJECTIVE Bilateral vestibular loss (BVL) is often diagnosed with great delay and an underlying cause is only identified in 50-80%. We measured horizontal and vertical semicircular canal function using the video-head-impulse test (vHIT) and hypothesized that specific vHIT-patterns may be linked to certain etiologies. METHODS We retrospectively analyzed 109 BVL-patients linked to aminoglycoside vestibulotoxicity (n=16), Menières disease (n=10), infectious inner-ear disorders (n=11), sensorineural hearing-loss (n=11), cerebellar-ataxia-neuropathy-vestibular-areflexia-syndrome (CANVAS, n=5), other causes (n=19) as well as those with unknown origin (n=47). Vestibulo-ocular reflex gains and cumulative saccade amplitudes were measured with vHIT, and the functional integrity of all semicircular canals was rated. RESULTS Overall, anterior canal hypofunction (n=86/218) was identified significantly (p<0.001) less often than horizontal (n=186/218) and posterior (n=194/218) hypofunction. Preserved anterior canal function was associated with aminoglycoside vestibulotoxicity, Menières disease and BVL of unknown origin, while no such sparing was found for inner-ear infections, CANVAS and sensorineural hearing loss. CONCLUSIONS Semicircular canal function in BVL shows disease-specific dissociations, potentially related to reduced vulnerability or superior recovery of the anterior canals. SIGNIFICANCE In patients with suspected BVL we recommend quantifying vHIT gains and saccade amplitudes for all semicircular canals as the pattern of canal hypofunction may help identifying the underlying disorder.

Cetuximab induced aseptic meningitis.

We report a 67-year-old man with recurrent advanced oropharyngeal squamous cell carcinoma who developed aseptic meningitis, with first symptoms arising approximately 9hours after the first administration of cetuximab, and review the literature to identify key signs and symptoms of this condition. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor which has been rarely associated with aseptic meningitis. Besides the case description, a MEDLINE search was performed. In five patients identified in the literature and our patient, the leading signs and symptoms included headache, neck stiffness and high fever developing within a few hours of the first cetuximab administration. Cerebrospinal fluid (CSF) analysis revealed severe pleocytosis (range: 528-2300/μl) with dominance of neutrophils (⩾87%). Clinical recovery within 1-2weeks was accompanied by normalization of CSF cell count within 4-7days. Re-challenge with cetuximab at a reduced dose caused recurrent aseptic meningitis in one of three patients. In summary, aseptic meningitis is a rare complication after first cetuximab exposure that the clinician should be aware of. CSF analysis is the key to diagnosis and recovery is usually complete within days to weeks after withdrawal of the drug. Re-challenge may be considered but bears the risk of recurrence.

Clinical Course, Radiological Manifestations, and Outcome of Pneumocystis jirovecii Pneumonia in HIV Patients and Renal Transplant Recipients

Background Pneumocystis jirovecii pneumonia (PCP) is a frequent opportunistic infection in immunocompromised patients. In literature, presentation and outcome of PCP differs between patients with human immunodeficiency virus (HIV) infection and renal transplant recipients (RTRs). Methods We conducted a cross-sectional study of patients with PCP based on the HIV and renal transplant registries at our institution. Radiological and clinical data from all confirmed PCP cases between 2005 and 2012 were compared. Results Forty patients were included: 16 with HIV and 24 RTRs. Radiologically, HIV patients had significantly more areas of diffuse lung affection (81% HIV vs. 25% RTR; p = 0.02), more ground glass nodules 5–10 mm (69% vs. 4%; p = <0.001) and enlarged hilar lymph nodes were found only in HIV patients (44%). Cough and dyspnea were the most common clinical signs (>80%) in both groups. Duration from illness onset to hospital presentation was longer in the HIV patients (median of 18 vs. 10 days (p = 0.02)), implying a less fulminant clinical course. Sixty percent of PCP cases in RTRs occurred >12 months after transplantation. Lengths of hospitalization, admission rates to the intensive care unit, and requirements for mechanical ventilation were similar. Outcome in both groups was favourable. Conclusions While important differences in radiological presentation of PCP between HIV patients and RTRs were found, clinical presentation was similar. PCP only rarely presented with fulminant respiratory symptoms requiring ICU admission, with similar results and outcomes for HIV patients and RTRs. Early diagnosis and treatment is mandatory for clinical success.

[Nalmefene and Opioid Withdrawal Syndrome: Analysis of the Global Pharmacovigilance Database for Adverse Drug Reactions].

Nalmefene (Selincro®) is a selective opioid receptor antagonist, licensed in April 2014 in Switzerland for the reduction of alcohol consumption in adults with a high drinking risk level. 200 reports of adverse drug reactions of nalmefene have been documented worldwide in the WHO global pharmacovigilance database between 7th March 1997 to 1st March 2015. In 21 cases (10,5%) nalmefene and an opioid were administered concomitantly, causing withdrawal symptoms. Until now, the regional pharmacovigilance center in Zurich received four cases of nalmefene combined with opioids. This combination should be avoided.

Treatment of gout in a renal transplant patient leading to severe thrombocytopenia

Allopurinol (AP) inhibits the xanthine oxidase, which may indirectly lead to myelotoxicity when used in combination with azathioprine (AZA).

Concomitant administration of rifampicin and oxcarbazepine results in a significant decrease of the active MHD metabolite of oxcarbazepine.

To the Editors: The prodrug oxcarbazepine is an antiepileptic agent structurally resembling carbamazepine but differing in its metabolism. Oxcarbazepine inhibits voltage-dependent sodium channels resulting in an interruption of the epileptical discharge [1]. Oxcarbazepine is extensively metabolized by the liver into the active metabolite 10-monohydroxy-carbazepine (MHD) via cytosolic keto-reductase enzymes. MHD is predominantly deactivated through uridine diphosphateglucuronyltransferase (UGT) into glucuronide conjugates and by oxidation into 10,11-dihydroxy-derivative (DHD, only about 4 %) [2]. Urinary excretion comprises of 49 % MHD glucuronides, 27 % MHD, 9 % oxcarbazepine glucuronides, and <1 % unchanged oxcarbazepine [3]. Oxcarbazepine and MHD inhibit cytochrome P 450 (CYP) 2C19 and induce CYP3A4 and CYP3A5 but lack the ability for autoinduction [4]. Strong enzyme inducers, such as carbamazepine, phenytoin, or phenobarbital are known to decrease the serum concentration of MHD by 13–40 % [5–8]. Rifampicin is another potent inducer of CYP enzymes, P-glycoprotein (P-gp), and UGT [9]. However, potential effects of rifampicin on the pharmacokinetics of oxcarbazepine are unknown. Here, we present a 33-year-old female (BMI 27.5 kg/m, active smoker) on long-term oxcarbazepine treatment at a daily dose of 1,200 mg for epilepsy. Due to therapy-resistant acne vulgaris, rifampicin 600 mg daily and clindamycin 300 mg b.i.d. were initiated. Therapeutic drug monitoring (TDM) of oxcarbazepine and MHD trough concentrations was conducted before, during, and after the course of antibiotic therapy on days 0, 3, 7, 14, 21, 35, 59, 83, and 92 (Fig. 1). Coadministration with rifampicin resulted in a significant decrease of MHD serum concentrations by 49% on day 7, while oxcarbazep ine concen t ra t ions remained s tab le . Oxcarbazepine dosing was adapted to maintainMHD concentrations within the therapeutic range. A 75 % increase of the initial oxcarbazepine dose (final daily dose 2,100 mg) was required to achieve similar MHD target concentrations during rifampicin treatment compared to baseline. After discontinuation of rifampicin, MHD serum concentrations increased despite an initial oxcarbazepine dose reduction. Finally, the oxcarbazepine dose could be reduced to baseline dosage of 1,200 mg resulting in similar MHD concentrations before the rifampicin treatment. The patient did not experience any epileptic seizure and adverse reaction during and after the period of coadministered rifampicin. This is the first report on coadministration of rifampicin and oxcarbazepine. To our knowledge, the exact mechanism of the interaction between oxcarbazepine and enzyme inducers is not known. MHD concentration-tooxcarbazepine dose ratio on day 7 (Fig. 1) was similar to previous results with other inducers [10]. Similar effects might play a role with rifampicin as the magnitude of the effect was comparable. However, a more pronounced decrease of MHD concentrations cannot be ruled out due to oxcarbazepine dose adjustments guided by TDM. Moreover, the effect on MHD concentrations might be dependent on the dose of rifampicin. Recently, MHD exposure was shown to be increased by 10 % during coadministration of the P-gp inhibitor verapamil [11]. Since rifampicin is known to induce P-gp, UGT, and CYP, a combination of different pharmacokinetic alterations, such * Stefan Weiler stefan.weiler@usz.ch

Shaking head means “no”

A 45-year-old man was admitted to the emergency department because of twitching of the head. The patient took a tablet of sumatriptan every 3–4 h because of increasing head pain after a car accident. Owing to depression, the patient was on long-term treatment with venlafaxine. The patient presented as hypertensive, tachycardic, with dyskinesia and spontaneous myoclonic movements of the right sternocleidomastoid muscle. In a CT scan of the head and cervical spine any fractures, bleeding or damage of the vessels after the accident could be ruled out. After discontinuation of all serotonergic agents, administration of lorazepam symptoms resolved 24 h after the last intake of sumatriptan. Serotonin syndrome is a clinical diagnosis, which requires a high-index of diagnostic suspicion. Clinical features include a broad spectrum of symptoms ranging from mild to life-threatening manifestations. Management is based on removal of precipitating drugs and symptomatic care including benzodiazepines.

Clinical manifestations, pathophysiology, treatment and outcome of inflammatory bowel diseases in older people

Approximately 10-20% of inflammatory bowel disease (IBD) cases are diagnosed after 60 years of age. Due to the high prevalence of conditions mimicking IBD at older age - including bowel disease associated with non-steroidal anti-inflammatory drugs, diverticulitis, and microscopic colitis - differential diagnosis of IBD among older adults is frequently delayed. Late-onset IBD is characterized by a predominance of colonic disease and an overall milder disease course; disease progression and new intestinal manifestations are rare. However, older patients are less able to tolerate inflammation and their risk of mortality from severe disease is increased. Management of late-onset IBD has been insufficiently studied since older adults are underrepresented in clinical trials and specific problems of older patients such as incontinence have not been addressed. To date, treatment generally follows the same principles as in the younger. However, older patients are at higher risk of severe adverse effects of the disease and its treatments, including bone and muscle loss, infections and lymphoma. Therefore, the safety profile of a given drug is of paramount importance in older patients with IBD. Colectomy with ileo-anal pouch anastomosis for refractory ulcerative colitis can be performed safely, although functional results may be inferior to those in middle-aged patients. To decrease mortality among older patients, a timely surgical intervention is important. Patients with late-onset IBD frequently develop colorectal carcinoma within 8 years of diagnosis; therefore, colorectal cancer screening immediately after diagnosis should be considered. Further, the clinical care of older patients with IBD needs to extend to overall health, including nutrition, vaccination, bone, muscle and mental health.

Emergency medicine in the extreme geriatric era: A retrospective analysis of patients aged in their mid 90s and older in the emergency department

In the coming years, older individuals will comprise an increasing share of emergency department (ED) admissions, due to the unprecedented and continuing demographic changes. The primary aim of the present study was to identify causes and risk factors for ED admission and hospitalizations in the oldest old.

Cementing the lungs

A 78 year old woman was admitted to the emergency department owing to recurrent syncope after lumbosacral vertebroplasty and cement screw …