Neologistic jargon aphasia and agraphia in primary progressive aphasia

The terms 'jargon aphasia' and 'jargon agraphia' describe the production of incomprehensible language containing frequent phonological, semantic or neologistic errors in speech and writing, respectively. Here we describe two patients with primary progressive aphasia (PPA) who produced neologistic jargon either in speech or writing. We suggest that involvement of the posterior superior temporal-inferior parietal region may lead to a disconnection between stored lexical representations and language output pathways leading to aberrant activation of phonemes in neologistic jargon. Parietal lobe involvement is relatively unusual in PPA, perhaps accounting for the comparative rarity of jargon early in the course of these diseases. (C) 2008 Elsevier B.V. All rights reserved

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

Teaching NeuroImages: Nonfluent variant primary progressive aphasia: A distinctive clinico-anatomical syndrome

A 66-year-old woman presented with 4 years of progressive speech difficulty. She had nonfluent speech with phonemic errors but intact single-word comprehension and object knowledge. Her grammar was impaired in both speech and writing, and she exhibited orofacial apraxia. A clinico-radiologic (see figure) diagnosis of nonfluent variant primary progressive aphasia was made

Teaching Neuro Images: Nonfluent variant primary progressive aphasia: A distinctive clinico-Anatomical syndrome

A 66-year-old woman presented with 4 years of progressive speech difficulty. She had nonfluent speech with phonemic errors but intact single-word comprehension and object knowledge. Her grammar was impaired in both speech and writing, and she exhibited orofacial apraxia. A clinico-radiologic (see figure) diagnosis of nonfluent variant primary progressive aphasia was made

TDP43 pathology in the brain, spinal cord, and dorsal root ganglia of a patient with FOSMN

OBJECTIVE: To describe the histopathologic features of a case of facial-onset sensory and motor neuronopathy (FOSMN). METHODS: We describe a postmortem examination performed on a 54-year-old man with FOSMN associated with personality change. RESULTS: Postmortem examination revealed TAR DNA-binding protein (TDP) 43 proteinopathy with widespread distribution. TDP43 pathology was seen in the neurons and glial cells and was most pronounced in the subthalamic nucleus followed by the spinal cord, including dorsal root ganglia, brainstem, and other deep cerebral nuclei. In the medial temporal lobe, neocortex and subcortical hemispheric white matter TDP43 pathologic inclusions were very rare. In contrast to TDP43 pathologies associated with typical amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD)–TDP, in this case, there were more frequent TDP43-positive oligodendroglial, coiled body–like cytoplasmic inclusions than neuronal inclusions. Neuronal cytoplasmic TDP43 inclusions with globular and skein-like morphology were seen in both anterior horn cells and dorsal root ganglia. No β-amyloid, α-synuclein, or significant hyperphosphorylated tau pathology was seen. CONCLUSION: This case provides further evidence that FOSMN is a neurodegenerative disease characterized by TDP43 pathology. Despite minimal cortical TDP43 pathology, the clinical features of the behavioral variant of FTD in this patient suggest that FOSMN may fall within or overlap with the FTD-ALS spectrum

Frontotemporal dementia

Frontotemporal dementia refers to a diverse group of conditions that collectively are a major cause of young onset dementia Frontotemporal dementia produces selective brain atrophy involving the frontal and temporal lobes, requiring brain magnetic resonance imaging for accurate diagnosis Clinically, these diseases present chiefly as progressive aphasia or as disintegration of personality and behaviour that may be misdiagnosed as a psychiatric disorder Up to around a quarter of cases arise from dominant mutations in one of three major causative genes Frontotemporal dementia is commonly associated with other neurological impairment, in particular parkinsonism or motor neurone disease Treatment remains supportive, but patients and families need extensive counselling, future planning, and involvement of social and mental health service

Molecular nexopathies: a new paradigm of neurodegenerative disease.

Neural networks provide candidate substrates for the spread of proteinopathies causing neurodegeneration, and emerging data suggest that macroscopic signatures of network disintegration differentiate diseases. However, how do protein abnormalities produce network signatures? The answer may lie with 'molecular nexopathies': specific, coherent conjunctions of pathogenic protein and intrinsic network characteristics that define network signatures of neurodegenerative pathologies. Key features of the paradigm that we propose here include differential intrinsic network vulnerability to propagating protein abnormalities, in part reflecting developmental structural and functional factors; differential vulnerability of neural connection types (e.g., clustered versus distributed connections) to particular pathogenic proteins; and differential impact of molecular effects (e.g., toxic-gain-of-function versus loss-of-function) on gradients of network damage. The paradigm has implications for understanding and predicting neurodegenerative disease biology

A novel A781V mutation in the CSF1R gene causes hereditary diffuse leucoencephalopathy with axonal spheroids

We report a family with a novel CSF1R mutation causing hereditary diffuse leucoencephalopathy with axonal spheroids. Family members presented with neuropsychiatric and behavioural symptoms, with subsequent development of motor symptoms and gait disturbance. MRI brain showed extensive white matter change with a frontal predominance and associated atrophy in two members of the family. Genetic testing revealed a novel mutation c.2342C>T (p.A781V) in the CSF1R gene in two brothers of the family. This report highlights the difficulties in diagnosing HDLS and discusses the indications for testing for mutations in the CSF1R gene

Teaching NeuroImages: Nonfluent variant primary progressive aphasia A distinctive clinico-anatomical syndrome

The Dementia Research Centre is grateful for the support of the NIHR Queen Square Dementia Biomedical Research Unit. The Article Processing Charge was paid by Wellcome Trust