The undiscovered syndrome: Macdonald Critchley's case of semantic dementia

Semantic dementia is a unique clinicopathological syndrome in the frontotemporal lobar degeneration spectrum. It is characterized by progressive and relatively selective impairment of semantic memory, associated with asymmetric antero-inferior temporal lobe atrophy. Although the syndrome became widely recognized only in the 1980s, descriptions of cases with typical features of semantic dementia have been on record for over a century. Here, we draw attention to a well documented historical case of a patient with features that would have fulfilled current consensus criteria for semantic dementia, as reconstructed from the notes made by her neurologist, Macdonald Critchley, in 1938. This case raises a number of issues concerning the nosology of the semantic dementia syndrome and the potential value of archived case material

The brain basis of musicophilia: evidence from frontotemporal lobar degeneration.

Musicophilia, or abnormal craving for music, is a poorly understood phenomenon that has been associated in particular with focal degeneration of the temporal lobes. Here we addressed the brain basis of musicophilia using voxel-based morphometry (VBM) on MR volumetric brain images in a retrospectively ascertained cohort of patients meeting clinical consensus criteria for frontotemporal lobar degeneration: of 37 cases ascertained, 12 had musicophilia, and 25 did not exhibit the phenomenon. The syndrome of semantic dementia was relatively over-represented among the musicophilic subgroup. A VBM analysis revealed significantly increased regional gray matter volume in left posterior hippocampus in the musicophilic subgroup relative to the non-musicophilic group (p < 0.05 corrected for regional comparisons); at a relaxed significance threshold (p < 0.001 uncorrected across the brain volume) musicophilia was associated with additional relative sparing of regional gray matter in other temporal lobe and prefrontal areas and atrophy of gray matter in posterior parietal and orbitofrontal areas. The present findings suggest a candidate brain substrate for musicophilia as a signature of distributed network damage that may reflect a shift of hedonic processing toward more abstract (non-social) stimuli, with some specificity for particular neurodegenerative pathologies

Musical tasks targeting preserved and impaired functions in two dementias.

Studies of musical abilities in dementia have for the most part been rather general assessments of abilities, for instance, assessing retention of music learned premorbidly. Here, we studied patients with dementias with contrasting cognitive profiles to explore specific aspects of music cognition under challenge. Patients suffered from Alzheimer's disease (AD), in which a primary impairment is in forming new declarative memories, or Lewy body disease (PD/LBD), a type of parkinsonism in which executive impairments are prominent. In the AD patients, we examined musical imagery. Behavioral and neural evidence confirms involvement of perceptual networks in imagery, and these are relatively spared in early stages of the illness. Thus, we expected patients to have relatively intact imagery in a mental pitch comparison task. For the LBD patients, we tested whether executive dysfunction would extend to music. We probed inhibitory skills by asking for a speeded pitch or timbre judgment when the irrelevant dimension was held constant or also changed. Preliminary results show that AD patients score similarly to controls in the imagery tasks, but PD/LBD patients are impaired relative to controls in suppressing some irrelevant musical dimensions, particularly when the required judgment varies from trial to trial

Delayed auditory feedback simulates features of nonfluent primary progressive aphasia.

The pathophysiology of nonfluent primary progressive aphasia (nfvPPA) remains poorly understood. Here, we compared quantitatively speech parameters in patients with nfvPPA versus healthy older individuals under altered auditory feedback, which has been shown to modulate normal speech output. Patients (n=15) and healthy volunteers (n=17) were recorded while reading aloud under delayed auditory feedback [DAF] with latency 0, 50 or 200 ms and under DAF at 200 ms plus 0.5 octave upward pitch shift. DAF in healthy older individuals was associated with reduced speech rate and emergence of speech sound errors, particularly at latency 200 ms. Up to a third of the healthy older group under DAF showed speech slowing and frequency of speech sound errors within the range of the nfvPPA cohort. Our findings suggest that (in addition to any anterior, primary language output disorder) these key features of nfvPPA may reflect distorted speech input signal processing, as simulated by DAF. DAF may constitute a novel candidate pathophysiological model of posterior dorsal cortical language pathway dysfunction in nfvPPA

Prevalence, clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand

A small but variable subgroup of patients with myasthenia gravis (MG) who have antibodies to muscle-specific kinase (MuSKAb-MG) can present with distinct phenotypes and are often treatment-resistant. The prevalence, clinical phenotypes and outcomes of treatment of patients with MuSKAb-MG in Thailand were determined. Eight (16.3%) of the 49 patients with generalized MG who were negative for acetylcholine receptor antibodies (AChRAb) were positive for muscle-specific kinase antibodies. Most patients had predominant oculobulbar features and respiratory failure occurred in three. At follow up, three out of the seven patients who underwent thymectomy were in complete stable remission and four had improved and were on reduced immunosuppression medication, suggesting a possible benefit of thymectomy. © 2012 Elsevier Ltd. All rights reserved

PID associated with fertility regulating agents. Task Force on Intrauterine Devices, Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization.

A WHO sponsored matched case-control study to examine the association between acute pelvic inflammatory disease (PID) and contraceptive use was conducted in 8 developing country and 4 developed country centres. 608 cases of acute febrile non-postpartum PID were individually matched with 1216 controls; 437 of the cases came from centres in developing countries and 171 from developed country centres. Among parous women the relative risks of a first episode of PID associated with current IUD use were 2.3 in developing and 4.1 in developed country centres. Nulliparous women in developed countries had a relative risk of 11.5, but the risks could not be estimated for nulliparous developing country women because there were insufficient IUD users. The high risk among nulliparous women was in part due to bias arising from probable differences in sexual activity in unmarried cases and controls. The risks for parous women aged 15-24 were 9.1 in developed and 2.9 in developing country centres. The risks of PID associated with current IUD use were much higher in women with a past history of PID. An increased PID risk was also found with past IUD use. Use of oral contraceptives or conventional contraceptives was associated with a reduced risk of first episode PID in parous but not in nulliparous women. Irrespective of contraceptive use, a past history of PID increased the risk of recurrent infection, and abortion was associated with an increased risk of first episode and recurrent PID. In conclusion, except for women under 25, the present study showed similar risks of PID related to contraceptive use, past infection or abortion in parous women from developed and developing country centres