Clinical and imaging characteristics of late onset mitochondrial membrane protein-associated neurodegeneration (MPAN).

Young onset dementias present significant diagnostic challenges. We present the case of a 35-year-old Kuwaiti man with social withdrawal, drowsiness, irritability, anxiety, aphasia, memory loss, hypereflexia, and Parkinsonism. Brain MRI showed bilateral symmetric gradient echo hypointensities in the globi pallidi and substantiae nigrae. Left cortical hypometabolism was seen on brain fluorodeoxyglucose positron emission tomography. A cortical brain biopsy revealed a high Lewy body burden. Genetic testing revealed a homozygous p.T11M mutation in the C19orf12 gene consistent with mitochondrial membrane protein-associated neurodegeneration. This is the oldest onset age of MPAN reported.

A young-onset frontal dementia with dramatic calcifications due to a novel CSF1R mutation.

Neuroimaging and genomic analysis greatly aid in the identification of young-onset dementia antemortem. We present the case of a 33-year-old female with a 2-year rapid decline to dementia and immobility marked by personality change, executive deficits including compulsions, attention deficit, apraxia, Parkinsonism, and pyramidal signs. She had unique and dramatic calcifications and confluent white matter changes on imaging and was found to have a novel mutation in the colony stimulating factor 1 receptor gene causing adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Here, we review ALSP and briefly discuss differential diagnoses.

Is therapeutic plasma exchange indicated for patients with gemcitabine-induced hemolytic uremic syndrome?

Atypical hemolytic uremic syndrome (aHUS) has been described as an uncommon complication of gemcitabine. In this review, we discuss the diagnosis of gemcitabine-induced aHUS (GiHUS) and the published experience with therapeutic plasma exchange (TPE). To illustrate GiHUS, we present a patient who developed hypertension and peripheral edema while receiving gemcitabine and subsequently was found to have thrombocytopenia, hemolytic anemia, renal failure, and normal ADAMTS-13 activity. Although laboratory parameters improved on suspending gemcitabine, they worsened after reinstitution of the drug. Thrombocytopenia and hemolysis ceased once the drug was permanently discontinued without therapeutic plasma exchange (TPE). The pathological characteristics of GiHUS suggest damage of the glomeruli endothelial lining, leading to occlusion by fibrin-rich thrombi. Among 26 patients described in the literature not treated with TPE, 56% recovered from GiHUS, whereas only 30% of 18 patients treated with TPE did. The difference in recovery rate may have been confounded by the severity of GiHUS as suggested by the rate of dialysis in each group: 10/26 (38%) patients who did not receive TPE were dialyzed compared with 11/18 (61%) of those who had plasma exchange. Thus, although the currently available evidence is not decisive for use or non use of TPE, we suggest that the most important therapeutic intervention in GiHUS is discontinuation of the drug. Apheresis medicine specialists should be aware of this specific type of aHUS and provide treatment advice based on the currently available evidence.