A pathology of the animal spirits – the clinical neurology of Thomas Willis (1621–1675) Part II – Disorders of intrinsically abnormal animal spirits

Thomas Willis (1621-1675), author of the classical work Cerebri Anatome (1664), was arguably the father of the modern era of neurology. His clinical neurology, as described in his Pathologiae Cerebri (1667) and De Anima Brutorum (1672), was largely derived from personal observations and not from traditional authorities and was based around his concept of the animal spirits, a fictitious entity in many ways analogous to the present day idea of the nerve impulse. This concept allowed him to develop a pathology of the animal spirits which embraced the whole content of the clinical neurology and psychiatry of his times. The anatomical and physiological background to Willis' concepts of animal spirit dysfunction, and those disorders he regarded as due to disturbed function of intrinsically normal animal spirits, have been dealt with in the previous part of this paper. The disorders he attributed to intrinsically abnormal animal spirits, dealt with in this part of the paper, comprised two categories. In one, the animal spirits possessed explosive properties, whilst in the other the abnormalities were non-explosive in their nature. The former category included epilepsy, hysteria and hypochondriasis, whilst the latter included mainly disorders now considered psychiatric e.g. delirium, melancholy, madness and stupidity. Willis' ideas about the pathogenesis of nervous system disorder seem never to have been generally accepted, partly because they appeared at a time when others were increasingly calling into question the existence of the animal spirits. Nevertheless, Willis' attempt to record and interpret all nervous system disease on the basis of disorder of function of a single underlying mechanism represents a formidable synthetic intellectual endeavour on the part of a very busy physician. (C) 2002 Elsevier Science Ltd. All rights reserved.

Leonard Bell Cox (1894-1976) - pioneer of Australian clinical neurology

The name of Leonard Bell Cox (1894-1976) will long be associated with a number of very significant areas in the intellectual and cultural life of the Australian State of Victoria. A quarter of a century after his death, his cultural achievements, and the enduring products of these achievements, continue to be celebrated in his native city, Melbourne. However his enormous contributions in these cultural fields were matched by his perhaps less widely known achievements in medicine, in particular in the neurosciences. In his time he not only pioneered the foundation and progressive development of the speciality of clinical neurology in Australia, but at the same time became a recognised world expert on the pathology of brain tumours.

A pathology of the animal spirits - the clinical neurology of Thomas Willis (1621-1675) Part I - Background, and disorders of intrinsically normal animal spirits

Thomas Willis (1621-1675), author of the classical work Cerebri Anatome (1664), was arguably the father of the modem era of neurology. As compared with his neuroanatomy, relatively little attention has been paid to Willis' clinical neurology, as described in his Pathologiae Cerebri (1667) and Do Anima Brutorum (1672), where he gave a structured account of disease of the nervous system as it was known in his day. His account was largely derived from personal observations and not from traditional authorities and was based around his concept of the animal spirits, a fictitious entity in many ways analogous to the present day idea of the nerve impulse. This concept allowed him to develop a pathology of the animal spirits which embraced the whole content of the clinical neurology and psychiatry of his times. The anatomical and physiological background to Willis! concepts of animal spirit dysfunction, and those disorders he regarded as due to disturbed function of intrinsically normal animal spirits (mainly headache, disorders of consciousness, apoplexy and palsy) are dealt with in the present paper. The disorders he attributed to inherently abnormal animal spirits are considered in a second part of the paper. (C) 2002 Elsevier Science Ltd. All eights reserved.

Development and standardization of the Self-regulation Skills Interview (SRSI): A new clinical assessment tool for acquired brain injury

The Self-regulation Skills Interview (SRSI) is a clinical tool designed to measure a range of metacognitive skills essential for rehabilitation planning, monitoring an individual's progress, and evaluating the outcome of treatment interventions. The results of the present study indicated that the SRSI has sound interrater reliability and test-retest reliability. A principle components analysis revealed three SRSI factors: Awareness, Readiness to Change, and Strategy Behavior. A comparison between a group of 61 participants with acquired brain injury (ABI) and a group of 43 non-brain-injured participants indicated that the participants with ABI had significantly lower levels of Awareness and Strategy Behavior, but that level of Readiness to Change was not significantly different between the two groups. The significant relationship observed between the SRSI factors and measures of neuropsychological functioning confirmed the concurrent validity of the scale and supports the value of the SRSI for post-acute assessment.

Clinical and molecular genetics of myoclonic-astatic epilepsy and severe myoclonic epilepsy in infancy (Dravet syndrome)

The majority of severe epileptic encephalopathies of early childhood are symptomatic where a clear etiology is apparent. There is a small subgroup, however, where no etiology is found on imaging and metabolic studies, and genetic factors are important. Myoclonic-astatic epilepsy (MAE) and severe myoclonic epilepsy in infancy (SMEI), also known as Dravet syndrome, are epileptic encephalopathies where multiple seizure types begin in the first few years of life associated with developmental slowing. Clinical and molecular genetic studies of the families of probands with MAE and SMEI suggest a genetic basis. MAE was originally identified as part of the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus (GEFS(+)). Recent clinical genetic studies suggest that SMEI forms the most severe end of the spectrum of the GEFS(+). GEF(+) has now been associated with molecular defects in three sodium channel subunit genes and a GABA subunit gene. Molecular defects of these genes have been identified in patients with MAE and SMEI. Interestingly, the molecular defects in MAE have been found in the setting of large GEFS(+) pedigrees, whereas, more severe truncation mutations arising de novo have been identified in patients with SMEI. It is likely that future molecular studies will shed light on the interaction of a number of genes, possibly related to the same or different ion channels, which result in a severe phenotype such as MAE and SMEI. (C) 2001 Elsevier Science B.V. All rights reserved.

Familial partial epilepsy with variable foci: Clinical features and linkage to chromosome 22q12

Background: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families. Methods: We describe the clinical features and performed a linkage analysis in a Spanish kindred and in a third French-Canadian family distantly related to the original pedigrees. Results: Onset of seizures was typically in middle childhood, and attacks were usually easy to control. Seizure semiology varied among family members but was constant for each individual. In some, a pattern of nocturnal frontal lobe seizures led to consideration of the diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The Spanish family was mapped to chromosome 22q (multipoint lod score, 3.4), and the new French-Canadian family had a multipoint lod score of 2.97 and shared the haplotype of the original French-Canadian families. Conclusions: Identification of the various forms of familial partial epilepsy is challenging, particularly in small families, in which insufficient individuals exist to identify a specific pattern. We provide clinical guidelines for this task, which will eventually be supplanted by specific molecular diagnosis. We confirmed linkage of FPEVF to chromosome 22q 12 and redefined the region to a 5.2-Mb segment of DNA.

A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping

Progressive myoclonus epilepsy (PME) has a number of causes, of which Unverricht-Lundborg disease (ULD) is the most common. ULD has previously been mapped to a locus on chromosome 21 (EPM1). Subsequently, mutations in the cystatin B gene have been found in most cases. In the present work we identified an inbred Arab family with a clinical pattern compatible with ULD, but mutations in the cystatin B gene were absent. We sought to characterize the clinical and molecular features of the disorder. The family was studied by multiple field trips to their town to clarify details of the complex consanguineous relationships and to personally examine the family. DNA was collected for subsequent molecular analyses from 21 individuals. A genome-wide screen was performed using 811 microsatellite markers. Homozygosity mapping was used to identify loci of interest. There were eight affected individuals. Clinical onset was at 7.3 +/- 1.5 years with myoclonic or tonic-clonic seizures. All had myoclonus that progressed in severity over time and seven had tonic-clonic seizures. Ataxia, in addition to myoclonus, occurred in all. Detailed cognitive assessment was not possible, but there was no significant progressive dementia. There was intrafamily variation in severity; three required wheelchairs in adult life; the others could walk unaided. MRI, muscle and skin biopsies on one individual were unremarkable. We mapped the family to a 15-megabase region at the pericentromeric region of chromosome 12 with a maximum lod score of 6.32. Although the phenotype of individual subjects was typical of ULD, the mean age of onset (7.3 years versus 11 years for ULD) was younger. The locus on chromosome 12 does not contain genes for any other form of PME, nor does it have genes known to be related to cystatin B. This represents a new form of PME and we have designated the locus as EPM1B.

Neurology of ciguatera

Ciguatera is a widespread ichthyosarcotoxaemia with dramatic and clinically important neurological features. This severe form of fish poisoning may present with either acute or chronic intoxication syndromes and constitutes a global health problem. Ciguatera poisoning is little known in temperate countries as a potentially global problem associated with human ingestion of large carnivorous fish that harbour the bioaccumulated ciguatoxins of the photosynthetic dinoflagellate Gambierdiscus toxicus. This neurotoxin is stored in the viscera of fish that have eaten the dinoflagellate and concentrated it upwards throughout the food chain towards progressively larger species, including humans. Ciguatoxin accumulates in all fish tissues, especially the liver and viscera, of at risk species. Both Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins are heat stable polyether toxins and pose a health risk at concentrations above 0.1 ppb. The presenting signs of ciguatera are primarily neurotoxic in more than 80% of cases. Such include the pathognomonic features of postingestion paraesthesiae, dysaesthesiae, and heightened nociperception. Other sensory abnormalities include the subjective features of metallic taste, pruritis, arthralgia, myalgia, and dental pain. Cerebellar dysfunction, sometimes diphasic, and weakness due to both neuropathy and polymyositis may be encountered. Autonomic dysfunction leads to hypotension, bradycardia, and hypersalivation in severe cases. Ciguatoxins are potent, lipophilic sodium channel activator toxins which bind to the voltage sensitive (site 5) sodium channel on the cell membranes of all excitable tissues. Treatment depends on early diagnosis and the early administration of intravenous mannitol. The early identification of the neurological features in sentinel patients has the potential to reduce the number of secondary cases in cluster outbreaks.

Location of innervation zones of sternocleidomastoid and scalene muscles - a basis for clinical and research electromyography applications

Objectives: Advances in surface electromyography (sEMG) techniques provide a clear indication that refinement of electrode location relative to innervation zones (IZ) is required in order to optimise the accuracy, relevance and repeatability of the sEMG signals. The aim of this study was to identify the IZ for the sternocleidomastoid and anterior scalene muscles to provide guidelines for electrode positioning for future clinical and research applications. Methods: Eleven volunteer subjects participated in this study. Myoelectric signals were detected from the sternal and clavicular heads of the stemocleidomastoid and the anterior scalene muscles bilaterally using a linear array of 8 electrodes during isometric cervical flexion contractions. The signals were reviewed and the IZ(s) were identified, marked on the subjects' skin and measurements were obtained relative to selected anatomical landmarks. Results: The position of the IZ lay consistently around the mid-point or in the superior portion of the muscles studied. Conclusions: Results suggest that electrodes should be positioned over the lower portion of the muscle and not the mid-point, which has been commonly used in previous studies. Recommendations for sensor placement on these muscles should assist investigators and clinicians to ensure improved validity in future sEMG applications. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.