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As with my previous writings on the neurology of literature, all the references used have been personally read. Indeed, I should hasten to stress that the prime motive in my reading has been a love of literature, a secondary gain being an insight into the way in which a variety of writers has viewed neurological disease. Some of the descriptions leave no doubt as to the condition being described: in other descriptions, I have used a degree of imagination! All the references to foreign texts have been read in translation., (Copyright © 2013 S. Karger AG, Basel.)

The confines of this chapter are necessarily arbitrary. Its limits are partly imposed by the extent of my reading (all the references have been read in full!) and partly by the restrictions of space - as a consequence of that restriction there are innumerable examples which I have been unable to cover. I have concentrated, though not exclusively, on the literature of the 19th century. There is much neurology in the modern novel, but the accessibility afforded by the internet and other sources to accounts of neurological symptoms and diseases allows a present-day author an access that can bypass personal experience. Of greater interest are those descriptions of neurological disorders which coincided with, or even ante-dated, their appearance in the medical literature. My reading has been in English, but has extended to works translated from Spanish, French, German and Russian. I have concentrated on a small group of neurological conditions whose descriptions are of particular interest in the depth of observation they display, a depth suggesting they have stemmed from first-hand experience. They are grouped under the headings of cerebrovascular disease, syncopal attacks and epilepsy., (Copyright (c) 2010 S. Karger AG, Basel.)

This study identifies by microautoradiography activated microglia/macrophages as the main cell type expressing the peripheral benzodiazepine binding site (PBBS) at sites of active CNS pathology. Quantitative measurements of PBBS expression in vivo obtained by PET and [(11)C](R)-PK11195 are shown to correspond to animal experimental and human post-mortem data on the distribution pattern of activated microglia in inflammatory brain disease. Film autoradiography with [(3)H](R)-PK11195, a specific ligand for the PBBS, showed minimal binding in normal control CNS, whereas maximal binding to mononuclear cells was found in multiple sclerosis plaques. However, there was also significantly increased [(3)H](R)-PK11195 binding on activated microglia outside the histopathologically defined borders of multiple sclerosis plaques and in areas, such as the cerebral central grey matter, that are not normally reported as sites of pathology in multiple sclerosis. A similar pattern of [(3)H](R)-PK11195 binding in areas containing activated microglia was seen in the CNS of animals with experimental allergic encephalomyelitis (EAE). In areas without identifiable focal pathology, immunocytochemical staining combined with high-resolution emulsion autoradiography demonstrated that the cellular source of [(3)H](R)-PK11195 binding is activated microglia, which frequently retains a ramified morphology. Furthermore, in vitro radioligand binding studies confirmed that microglial activation leads to a rise in the number of PBBS and not a change in binding affinity. Quantitative [(11)C](R)-PK11195 PET in multiple sclerosis patients demonstrated increased PBBS expression in areas of focal pathology identified by T(1)- and T(2)-weighted MRI and, importantly, also in normal-appearing anatomical structures, including cerebral central grey matter. The additional binding frequently delineated neuronal projection areas, such as the lateral geniculate bodies in patients with a history of optic neuritis. In summary, [(11)C](R)-PK11195 PET provides a cellular marker of disease activity in vivo in the human brain.

We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.

The initial treatment for trigeminal neuralgia is medical. Carbamazepine is the drug of choice. If the patient proves to be intolerant of carbamazepine, a number of second-line drugs are available, though data on their relative efficacy are nonexistent. Phenytoin, baclofen, clonazepam, and sodium valproate are all worthy of consideration. Oxcarbazepine may be as effective as carbamazepine, but its availability is limited. Newer agents being tried in this condition include lamotrigine and gabapentin. Their comparative value has not been established. For patients resistant to or intolerant of drug therapy, interventional or surgical procedures are necessary. For younger, fit patients, particularly with involvement of the first division or all three divisions of the nerve, microvascular decompression is recommended. For older patients, for those not shown to have microvascular cross-compression, and for those not willing to undergo craniectomy, radiofrequency thermal rhizotomy is probably the next treatment of choice. Dogmatic recommendations are not appropriate in the absence of truly comparable data. Other techniques to be considered, if thermal rhizotomy is unsuccessful, include glycerol rhizotomy, balloon compression, partial sensory trigeminal rhizotomy, and peripheral neurectomy. The choice is given in no particular order. Patients offered such treatments require data on the track record of the relevant institution in performing that procedure. Stereotactic radiosurgery is still being evaluated for this condition. Because the associated morbidity is very low, it may become the treatment of choice for the elderly frail patient if longer-term follow-up establishes its continuing benefit.

Purpose: Lamotrigine is an effective add-on therapy against a range of epileptic seizure types. Comparative studies with carbamazepine (CBZ) as monotherapy in newly diagnosed epilepsy suggest similar efficacy. In this study, lamotrigine (LTG) and phenytoin (PHT) are compared., Methods: In a double-blind parallel-groups study, 181 patients with newly diagnosed untreated partial seizures or secondarily or primary generalised tonic-clonic seizures were randomised to two treatment groups. One group (n = 86) received LTG titrated over 6 weeks from a starting dose of 100 mg/day. The other (n = 95) received PHT titrated from 200 mg/day. Treatment continued for < or =48 weeks., Results: The percentages of patients remaining on each treatment and seizure free during the last 24 and 40 weeks of the study, and times to first seizure after the first 6 weeks of treatment (dose-titration period), did not differ significantly between the treatment groups. These were measures of efficacy. Time to discontinuation, a composite index of efficacy and safety, likewise did not distinguish between treatments. Adverse events led to discontinuation of 13 (15%) patients from LTG and 18 (19%) from PHT. The adverse-event profile for LTG was dominated by skin rash [discontinuation of 10 (11.6%) patients compared with five (5.3%) from PHT] rather than central nervous system side effects: asthenia, somnolence, and ataxia were each significantly more frequent in the PHT group. The high rate of rash with LTG was probably due to the high starting dose and may be avoidable. A quality-of-life instrument, the SEALS inventory, favoured LTG. Patients taking PHT showed the biochemical changes expected of an enzyme-inducing drug, whereas those taking LTG did not., Conclusions: LTG and PHT monotherapy were similarly effective against these seizure types in patients with newly diagnosed epilepsy. LTG was better tolerated, more frequently causing rash, but with a lower incidence of central nervous system side effects.

Both achalasia and Hirchsprung's disease arise from defects of innervation of the oesophagus and distal large bowel respectively. Their consequences are confined to disorders of motility in the relevant part of the gastrointestinal tract. Many neurogenic and primary muscle disorders are associated with abnormalities of gut motility. Stroke, even when unilateral, is commonly associated with dysphagia. Transcranial magnetoelectric stimulation has established that the pharyngeal phase of swallowing tends to receive its innervation principally from one hemisphere. In many neurological disorders, dysphagia is only one part of the clinical picture but in some--for example, the Chiari malformation--dysphagia may be the sole or major feature. Disturbances of small and large bowel motility, when seen in neurogenic disorders, are associated with autonomic neuropathy and are particularly common in diabetes mellitus. Primary muscle disorders can lead to dysphagia (for example, with polymyositis or oculopharyngeal dystrophy) or defects of large bowel motility (for example, with Duchenne's muscular dystrophy). Primary gut disorders particularly associated with neurological disease include pernicious anaemia, nicotinamide and thiamine deficiencies, selective vitamin E deficiency, and coeliac disease. Inflammatory bowel disease is associated with thromboembolic complications which may include the CNS, inflammatory muscle disease, and abnormalities on MRI of the brain of uncertain relevance. Whipple's disease is a rare condition which sometimes is largely or entirely confined to the CNS. In such cases, a particular neurological presentation can indicate the diagnosis.

This study addressed two questions; first, whether the supranormal adherence of blood lymphocytes from patients with multiple sclerosis (MS) to endothelial cell monolayers treated with tumour necrosis factor-alpha (TNF alpha) was a feature common to other inflammatory disorders; and second, whether the adherence properties of blood lymphocytes from MS patients were related to changes in disease activity and to levels of circulating TNF alpha and soluble adhesion molecules. In the first part of the investigation, lymphocytes from 14 patients with MS were more adherent to TNF alpha-treated endothelial cells (P < 0.01) than those from healthy controls, whereas the adherence properties of lymphocytes from 12 patients with rheumatoid arthritis, eight patients with psoriasis and ten patients with neurological diseases other than MS were normal. In the second phase of the work, measurement of the adhesive properties of lymphocytes isolated at monthly intervals from a further six MS patients over a 5-8 month period, found that changes in binding to TNF alpha-treated endothelial cells, directly paralleled changes in circulating levels of TNF alpha (r = 0.77; P < 0.001) and soluble vascular cell adhesion molecule-I (sVCAM-1) r = 0.67; P = 0.001). An increase in disease activity, measured by T2-weighted and gadolinium-enhanced magnetic resonance imaging of the central nervous system (CNS), occurred in two patients and was associated with heightened lymphocyte adhesiveness and a rise in serum TNF alpha levels. Further analysis of the 34 serum samples from the six MS patients revealed a direct relationship between the concentration of sL-selectin and soluble intercellular adhesion molecule-I (sICAM-I) (r = 0.65; P < 0.001) and between sL-selectin and sTNF alpha (r = 0.42; P < 0.02). These findings support the view that disease activity in MS is associated with an increased adhesive interaction of blood lymphocytes with vascular endothelium at inflammatory sites within the CNS.

Two patients with presumed encephalitis lethargica are presented with clinical features suggestive of two forms of the disease described by Von Economo: One patient had a psychosis and a mute-akinetic syndrome associated with myoclonus. The second patient presented with a psychosis and fever, developing severe dyskinesias involving the mouth, trunk and limbs, together with respiratory irregularities and presumed hypothalamic disturbance and disturbance of consciousness. In both cases, initial cerebrospinal fluid (CSF) examination revealed an elevated white cell count (predominantly lymphocytes), elevated protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT) brain scan was normal but in both cases EEG revealed diffuse slow wave activity. A 18F-Dopa positron emission tomography (PET) scan in case 2 was normal. The medical management of both patients is discussed. In case 1, L-Dopa improved the akinesia, while the myoclonus responded to clonazepam. In case 2, the severe dyskinesias failed to respond to a number of drugs, and she ultimately required paralysis to relieve her almost continuous movements. Both patients responded rapidly and dramatically to intravenous methylprednisolone. We suggest that steroid treatment should be considered in the acute phase of patients with features suggestive of encephalitis lethargica.

Two patients are described with clinical and neuroimaging features consistent with a diagnosis of multiple system atrophy (MSA). The patients are unusual in that facial myokymia became apparent clinically at some stage in their illness. In each patient, the nature and severity of the involuntary facial movements evolved over the course of the illness. Electrophysiologically the movement pattern was consistent with myokymia, and studies of blink-reflex responses suggested that the myokymic discharges were of brainstem origin. Involuntary facial movements described as facial action myoclonus with electrical characteristics consistent with myoclonus have been described previously in hereditary olivopontocerebellar atrophy (OPCA). Our report describes electrical and clinical features of facial myokymia in MSA with electrical features suggesting hyperexcitability of the facial motorneurons in the brainstem. Such myokymic movements may occur more frequently in MSA than previously recognised but may be missed clinically because of their evolving nature.

This study investigated the adherent properties and adhesion molecule expression of blood mononuclear cells (MNC) from a total of 84 patients with multiple sclerosis (MS). The MNC from MS patients were significantly more adherent than cells from normal healthy subjects to endothelial monolayers pretreated with 0.01 U/ml TNF-alpha (103% increase; P = 0.002), 0.1 U/ml TNF-alpha (80% increase; P < 0.01) and 1.0 U/ml TNF-alpha (41% increase; P < 0.02), and to endothelium pretreated with 10 U/ml IL-1 beta (44% increase; P < 0.05) and 100 U/ml interferon-gamma (IFN-gamma) (100% increase; P < 0.05). This augmented adhesion was a property of the lymphocytes, in particular CD4+ cells, and was inversely related to the time of onset of clinical relapse. The percentage of lymphocytes bearing the adhesion molecules CD49d, CD29 and CD62L was increased in MS blood, but the level of CD29 and CD62L expression was reduced. We infer that circulating lymphocytes in MS are predisposed to cross endothelial barriers at sites where inflammation has already commenced.

Carotid surgery was performed urgently on 22 occasions out of 300 (7%). Of 15 patients with progressing stroke, in all, progression of stroke was arrested. Six patients recovered virtually completely and eight had improving neurological deficit after surgery, i.e. 14 of 15 (93%) benefitted. The other patient had arrest of stroke for a week and then suffered ipsilateral stroke. Of the seven patients operated upon for crescendo transient ischaemic attacks, five had no deficit after surgery or further attacks. The sixth patient had no further attacks but was found to have a tiny, neurological deficit. In these six patients (87%), surgery was greatly beneficial. The remaining patient had a fatal stroke following operation.