Late-onset mitochondrial encephalopathy with lactic acidosis and stroke-like episodes and the role of serial imaging.

Mitochondria are essential for human metabolic function. Over 350 genetic mutations are associated with mitochondrial diseases, which are inherited in a matrilineal fashion. In mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), defective mitochondrial function and resultant impaired cellular energy production compromise vascular perfusion in affected tissues. Early diagnostic criteria suggested the diagnosis should be considered in those under 40. However, a broader range of phenotypes are now recognised, including those that present for the first time later in life. The primary presenting feature in MELAS is a stroke-like episode invariably resulting in patients undergoing neuroradiological imaging. We present a case of a woman with a first presentation of a stroke-like episode and seizures in her 40s who was eventually diagnosed with MELAS. We detail her clinical presentation, treatment and diagnosis, emphasising the role of serial imaging in her diagnosis.

Adjunctive brivaracetam in focal and generalized epilepsies: A single-center open-label prospective study in patients with psychiatric comorbidities and intellectual disability.

Clinical studies suggest that the antiepileptic drug (AED) brivaracetam (BRV) is associated with fewer behavioral and psychiatric adverse events (AEs) compared with levetiracetam (LEV) in treating epilepsy. There are, however, few comparative studies of treatment-emergent AEs between patients on BRV with preexisting psychiatric or behavioral comorbidities to those without. Our study compared longer-term tolerability over a 26-month period between these patient groups and assessed the overall efficacy of BRV as add-on therapy. Patients with intellectual disabilities in whom the prevalence of epilepsy is higher, are often excluded from randomized controlled trials, and our study further assessed comparative effectiveness between this patient group and those with normal range intellect. We collected prospective data on 134 patients prescribed add-on BRV for epilepsy at a tertiary UK center over a 26-month period. All patients had previously received LEV. Sixty-three patients were on LEV at the start of the data collection period. Levetiracetam was withdrawn and switched to BRV in 39 patients because of inefficacy and 24 patients because of behavioral or psychiatric side effects. Seventy-three patients (54%) had a preexisting psychiatric or behavioral disorder compared with 64 patients (46%) without. The retention rate at last follow-up [mean: 11 months (0.5-26 months)] was 60% in the psychiatric/behavioral disorders group versus 67% in those without (p = 0.68). Forty-one patients had diagnosed intellectual disabilities. The retention rate was 66% in this group versus 62% in patients without intellectual disabilities (p = 0.36). The commonest treatment-emergent AEs were somnolence (26%), aggression (23%), and depression (9%). There were similar frequencies reported for these specific events across the groups. The proportion with a 50% responder rate was 29% in patients with focal epilepsy and 47% in patients with generalized and combined focal and generalized epilepsies. However, fifteen patients (11%) reported increased seizure activity leading to withdrawal of treatment. This study showed evidence that BRV may be an effective adjunctive therapy in patients with drug-resistant focal or generalized epilepsies whose seizures have previously not responded or tolerated LEV therapy. We demonstrated a higher incidence of treatment-emergent AEs leading to lower retention rates compared with previous studies across all patient groups. There were, however, no significant differences in tolerability between patients with preexisting psychiatric or behavioral comorbidities, or intellectual disability to those without.

Erdheim-Chester Disease: Case Report with Aggressive Multisystem Manifestations and Review of the Literature.

Erdheim-Chester disease (ECD) is an extremely rare and aggressive form of non-Langerhans cell histiocytosis. ECD usually presents with bone pain in adults aged 40-60. Its etiology is unknown but it is thought to be either a reactive or neoplastic disorder. Recently, mutation of the proto-oncogene BRAF (BRAFV600E) has been found in more than 50% of cases. The multisystemic form of ECD is associated with significant morbidity, which may arise due to histiocytic infiltration of critical organ systems. The common sites of involvement are the skeleton, central nervous system, cardiovascular system, lungs, retroperitoneum, and skin. Current available treatment is interferon alpha as the first line of treatment. Treatment with other agents is based on anecdotal case reports. Cladribine, anakinra, and vemurafenib (BRAF inhibitor) are currently advocated as promising second-line treatments for patients whose response to interferon alpha is unsatisfactory. Herein, we are reporting a middle-aged Saudi male patient with an aggressive type of ECD and highlighting the clinical, radiological, and pathological manifestations associated with ECD and the various treatment options and patient follow-up.

Guillain-Barre syndrome associated with Norovirus infection.

The authors describe a case of Guillain-Barre syndrome after the diarrhoeal infection due to Norovirus. Many infections have been described most notably Campylobacter jejuni. To our knowledge a connection to Norovirus has not been described in the world literature. The authors speculate on why this may be so.

Methotrexate-induced acute leukemia: report of three cases and review of the literature.

For many years, methotrexate has been used in the treatment of certain chronic medical disorders e.g. rheumatoid arthritis and psoriasis as well as a number of malignant disorders e.g. acute lymphoblastic leukemia, certain types of lymphoma and breast carcinoma. Its use has been associated with various systemic toxicities and complications. The association between methotrexate therapy and the development of lymphoma and pseudolymphoma is well established. In patients treated with methotrexate, the development of leukemia has been attributed to either the primary disorder e.g. rheumatoid arthritis or to other drugs used concomitantly e.g. cyclophosphamide. Reported here are two patients with rheumatoid arthritis and one patient with psoriasis treated with low dose methotrexate for variable periods of time. Two of these patients developed acute myeloid leukemia on myelodysplastic syndrome background, while the third patient developed pre-B acute lymphoblastic leukemia that expressed few myeloid markers and had a positive philadelphia chromosome. To our knowledge, these are the first reported cases of methotrexate-induced acute leukemia.