Björn Brådvik

Disturbances of speech prosody following right hemisphere infarcts.

ABSTRACT The ability to perceive and express emotional, as well as number of linguistic prosodic qualities of speech was tested in 20 Swedish‐speaking patients with right‐sided cortical, as well as purely subcortical brain infarcts, and in 18 normal controls. The infarcts were assessed by clinical neurological examination, and by CT, EEG, and measurements of regional cerebral blod flow (rCBF). In the patients the identification of emotional messages was disturbed, as well as the identification and production of several linguistic prosodic qualities. The study supports the claim that prosodic impairment could be linguistic in nature, and not secondary to affective disorder. The total degree of anatomical and functional disturbance of the right hemisphere played a role for both the ability to identify emotional messages and for identification of two of the linguistic prosodic qualities tested. However, it was not possible to find support for the hypothesis that the organization of prosody in the right hemisphere mirrors that of propositional speech on the left side.

Hereditary myopathy with early respiratory failure associated with a mutation in A-band titin

Hereditary myopathy with early respiratory failure and extensive myofibrillar lesions has been described in sporadic and familial cases and linked to various chromosomal regions. The mutated gene is unknown in most cases. We studied eight individuals, from three apparently unrelated families, with clinical and pathological features of hereditary myopathy with early respiratory failure. The investigations included clinical examination, muscle histopathology and genetic analysis by whole exome sequencing and single nucleotide polymorphism arrays. All patients had adult onset muscle weakness in the pelvic girdle, neck flexors, respiratory and trunk muscles, and the majority had prominent calf hypertrophy. Examination of pulmonary function showed decreased vital capacity. No signs of cardiac muscle involvement were found. Muscle histopathological features included marked muscle fibre size variation, fibre splitting, numerous internal nuclei and fatty infiltration. Frequent groups of fibres showed eosinophilic inclusions and deposits. At the ultrastructural level, there were extensive myofibrillar lesions with marked Z-disc alterations. Whole exome sequencing in four individuals from one family revealed a missense mutation, g.274375T>C; p.Cys30071Arg, in the titin gene (TTN). The mutation, which changes a highly conserved residue in the myosin binding A-band titin, was demonstrated to segregate with the disease in all three families. High density single nucleotide polymorphism arrays covering the entire genome demonstrated sharing of a 6.99 Mb haplotype, located in chromosome region 2q31 including TTN, indicating common ancestry. Our results demonstrate a novel and the first disease-causing mutation in A-band titin associated with hereditary myopathy with early respiratory failure. The typical histopathological features with prominent myofibrillar lesions and inclusions in muscle and respiratory failure early in the clinical course should be incentives for analysis of TTN mutations.

Hereditary myopathy with early respiratory failure: occurrence in various populations

Objective Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort. Methods DNA samples of all currently known families with HMERF without molecular genetic cause were obtained from 12 families in seven different countries. Clinical, histopathological and muscle imaging data were collected and five biopsy samples made available for further immunohistochemical studies. Genotyping, exome sequencing and Sanger sequencing were used to identify and confirm sequence variations. Results All patients with clinical diagnosis of HMERF were genetically solved by five different titin mutations identified. One mutation has been reported while four are novel, all located exclusively in the FN3 119 domain (A150) of A-band titin. One of the new mutations showed semirecessive inheritance pattern with subclinical myopathy in the heterozygous parents. Typical clinical features were respiratory failure at mid-adulthood in an ambulant patient with very variable degree of muscle weakness. Cytoplasmic bodies were retrospectively observed in all muscle biopsy samples and these were reactive for myofibrillar proteins but not for titin. Conclusions We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.

Do single right hemisphere infarcts or transient ischaemic attacks result in aprosody

The ability to perceive and express prosodic qualities of speech was tested in 21 patients with a single focal ischaemic disturbance of the right hemisphere, 14 patients having an infarct and 7 transient ischaemic attacks, and in 21 age‐matched normal controls. All patients were predominantly right‐handed. None showed signs of aphasia. Pure tone audiometry showed acceptable hearing for speech. The cerebral lesions were assessed by clinical neurologic examination, and by CT, EEG and measurement of regional cerebral blood flow (rCBF) using intravenous 133‐xenon. The prosodia test included items testing: the ability to perceive accentual and emotional qualities of speech, and the ability to express and vary such qualities. The test did not discriminate between the patients and the controls, although some patients had large right‐sided lesions. This negative finding indicates that aprosody in patients with brain lesions appears more difficult to detect than has previously been assumed. Highly sensitive tests are most likely required.

Spatial impairment following right hemisphere transient ischaemic attacks in patients without carotid artery stenosis

ABSTRACT— Neuropsychological testing was performed on: 10 right‐handed patients who had had 1–4 right hemisphere transient ischaemic attacks (TIAs), 10 normal controls, 10 house painters with long‐term exposure to organic solvents, and 10 patients with liver cirrhosis. The subjects in each group were matched for age and education. No TIA patient had significant internal carotid artery stenosis, and CT was normal except in one patient, although magnetic resonance imaging (MRI) performed 3 years after the testing was abnormal in 4/8 cases. No patient reported additional distinct TIAs during the period between neuropsychological testing and MRI. The TIA patients showed lateralized signs of spatial impairment, whereas the cirrhotics and also (but to a lesser degree) the house painters showed signs of diffuse cerebral dysfunction. The study shows that hemispheric TIAs in patients without significant internal carotid artery stenosis may result in persistent focal cognitive impairment. This can be demonstrated with sensitive neuropsychological instruments even when MRI is normal.

Spatial and Perceptual Impairment Related to Cortical Cerebral Blood Flow and EEG in Deep White Matter Infarcts of the Right Hemisphere

A study was performed in order to investigate how infarcts located in the white matter of the right hemisphere may affect processing of spatial and perceptual abilities. A battery of neuropsychological tests was applied to 7 right-handed patients with CT-verified infarcts of the right internal capsule or periventricular white matter. Examinations were performed 1-3 weeks post stroke and 3-7 months later. The patients were assessed by neurological examinations, EEG, and cortical regional cerebral blood flow (rCBF) measurements. This study suggested that deep white matter infarcts of the right hemisphere may result in persistent spatial impairment in the absence of decreased cortical rCBF. Perception was disturbed in cases of low mean cortical CBF of both hemispheres.

Autosomal dominant cerebellar ataxia with slow ocular saccades, neuropathy and orthostatism: A novel entity?

BACKGROUND We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause. METHODS Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing. RESULTS The disorder presented as a balance and gait disturbance starting between 16 and 47 years of age. Cerebellar ataxia progressed slowly over the course of decades, and MRI showed mild to moderate cerebellar atrophy. Sensory axonal polyneuropathy was the most prominent additional feature and occurred in all patients examined. Autonomic neuropathy caused pronounced orthostatic dysregulation in at least four patients. Several affected members showed muscle wasting, and mild upper or lower motor neuron signs were documented. Patients had no nystagmus but slow or hypometric horizontal saccades and ocular motor apraxia. Cognition remained unimpaired, and there were no non-neurological disease manifestations. The disorder affected men and women in successive generations in a pattern compatible with autosomal dominant inheritance without evidence of anticipation. A second family where 7 members had very similar symptoms was identified and its origin traced back to the same village in southern Sweden as that of the first familys ancestors. All relevant known genetic causes of cerebellar ataxia were excluded by a novel next-generation sequencing approach. CONCLUSION We present two probably related Swedish families with a characteristic and novel clinical syndrome of cerebellar ataxia and sensory polyneuropathy. The study serves as a basis for the mapping of the underlying genetic cause.

Figures of speech and context awareness following right hemisphere infarcts.

The ability to interpret figures of speech was tested in nineteen patients with right hemisphere damage (RDH) and in seventeen controls. All subjects were presented fifteen expressions with metaphoric meanings and asked to select one of three pictures; one illustrating the literal meaning of the expression, one the metaphoric meaning and one a noun in the expression. RHD patients were expected to have problems in interpreting the metaphoric expressions but the hypothesis that the RHD group would select the literal picture more often than the controls was rejected. The groups differed, however, in the distribution of non-metaphoric answers, and in the way the tasks were solved. The performance by the RHD patients may reflect deficient awareness of the context.