Long-Term Survival after Progressive Multifocal Leukoencephalopathy in a Patient with Primary Immune Deficiency and NFKB1 Mutation.

PURPOSE: To describe the development of progressive multifocal leukoencephalopathy (PML) in a patient with primary immune deficiency (PID) due to a NFKB1 (nuclear factor kB subunit 1) mutation, who was treated successfully with a combination of mirtazapine and mefloquine. METHODS: We've based the treatment of our patient on literature research and provide a review of PML in CVID patients. RESULTS: Only a few reports have been published on the occurrence of PML in PID. PML is mainly observed in patients with reduced cellular immunity, which was not the case in our patient. Successful treatment options in this population are limited. Though severely disabled, our patient still survives, more than 4 years after symptom onset and shows consistent improvement on MRI (magnetic resonance imaging) and CSF (cerebrospinal fluid) analysis. CONCLUSION: We conclude that some patients with PML might be treatable and can show long-term survival although neurological deficits remain. Involvement of humoral immunity in the pathogenesis of PML as well as the possible role of NFKB1 mutations in response to specific pathogens deserves further investigation.

Posterior fossa syndrome in adults: a new case and comprehensive survey of the literature.

Although the posterior fossa syndrome (PFS) can be considered as an aetiologically heterogeneous condition affecting children and adults, it most often occurs in paediatric patients after cerebellar tumour surgery. In patients with a tumoural aetiology, the syndrome is typically characterised by a short symptom-free postoperative period followed by mutism of variable duration and behavioural and affective changes. More than 200 paediatric cases have been described but reports of adult patients are extremely rare. This paper discusses PFS in adults on the basis of a comprehensive literature survey and describes the pre- and postoperative findings in a new adult patient. In the preoperative phase, cognitive, behavioural and affective abnormalities were identified, matching a diagnosis of cerebellar cognitive affective syndrome (CCAS) (Schmahmann and Sherman, 1998; Schmahmann, 2004). The immediate postoperative course was characterised by prefrontal-like behavioural and affective abnormalities, peduncular hallucinations and confusion evolving to psychosis. Akinetic mutism subsequently developed, lasted for 12 days and then alternated with episodes of diminished responsiveness in which pathological laughing and crying (PLC) occurred. Akinetic mutism resolved after treatment with a non-ergoline dopamine-agonist but CCAS persisted during longitudinal follow-up. From a semiological point of view "relapsing-remitting akinetic mutism" and PLC in our patient might add relevant information to current insights in the clinical expression of the PFS. As evidenced by a close parallelism between single photon emission computed tomography (SPECT) and clinical findings, CCAS as well as PFS seem to reflect functional disruption of the cerebello-cerebral network involved in cognitive, behavioural and affective functions. These findings may indicate that both syndromes share overt semiological resemblances and a common pathophysiological substrate. Consequently, CCAS and PFS may both be regarded as cerebellar-induced clinical conditions showing different aspects of a spectrum that range in degree of severity and symptom duration.

Grammar disruption in a patient with Neuro-Sweet syndrome.

This paper for the first time reports detailed neurolinguistic findings in a patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of central nervous system (CNS) involvement primarily consisted of a selective grammar deficit restricted to spontaneous speech. On MRI a left prefrontal ischemic stroke (superior part BA 6) and two small subcortical left parietal infarctions were found. Neurolinguistic analyses, however, did not reveal a profile consistent with any observations of agrammatism caused by structural damage to the language areas critically involved in grammatical processing. It is hypothesized that selectively distorted grammar might reflect disruption of the frontosubcortical network involved in language processing. Prefrontal neurobehavioral abnormalities associated with functional disruption of the inferior medial frontal regions as demonstrated by SPECT, additionally suggest that agrammatic symptoms may be linked to a higher-level cognitive disorder following encephalopathic CNS involvement.