Global burden of neurological disorders

Public health is about the prevention of disease and the promotion of healthy living. Public health necessarily focuses on the community and groups of people; this is in contrast to the doctor who focuses on the patient. However, they both represent two ends of the same spectrum, one dealing with disease at population level, and the other dealing with disease at individual level. This chapter briefly outlines some of the basic principles of public health and their relationship to neurological disorders and health care delivery. The student should aim to be able to define incidence, prevalence and mortality rates and to understand disease burden and its measurement and prevention with particular regard to neurological disorders.

MEASUREMENT OF DISEASE

Disease occurrence

The simplest measurement of any disease is how common it is or the frequency of the disease in a community. In order to answer that question accurately, public health has first to be able to define and diagnose the disease, according to certain criteria and then measure its frequency in relation to the size of population in which the disease occurs or cases arise. This information is essential for public health planning and implementation. The science and art of gathering such information are the instruments of public health, much in the same way as the neurology history and examination are the instruments used for clinical neurology. The parameters used most frequently to report information on disease are the incidence, prevalence and mortality rates.

Incidence rate

Incidence rate is the most accurate method of measuring the frequency of a disease. The incidence rate is the number of new cases occurring in a defined population over a period of time. Measuring incidence over a period of time in a defined population gives an accurate measurement of disease frequency. Incidence measured over a year can be used to obtain the annual incidence of the disease. The annual incidence of the disease will include all new cases, or events occurring in the defined population during one year, including those who die soon after getting the disease, and those who recover from their disease. Incidence is measured as a rate, since it is always necessary to specify the time of observation.

Movement disorders occur mainly because of disease of the basal ganglia and its central connections. Drugs may also cause them. They are characterized as those with too little movement or hypokinetic disorders as occurs in Parkinson's disease or with too much movement or hyperkinetic disorders as occur in tremor, dystonia and chorea. The most common overall movement disorder is tremor and the most common major movement disorder is Parkinson's disease (PD). This chapter outlines the main movement disorders and also motor neurone disease. The student should aim to be familiar with their main clinical features and management.

PARKINSON's DISEASE (PD)

Parkinson's disease is a progressive neurodegenerative disorder characterized by four key clinical features: tremor, rigidity, poverty of movement also known as bradykinesia or akinesia, and loss of normal posture with a tendency for falls (Figs. 14.1 & 2). PD occurs all over the world affecting >1% of the population >65 years in high income countries. PD also occurs in Africa but may be less frequent there with lower reported age adjusted prevalence rates of 40–67/100,000. Males and females are both equally affected. PD typically begins in the age group 50–60 years and then occurs with increasing frequency in older age groups. PD may also affect a younger age group <40 yrs (5–10%). Juvenile onset PD (<20 yrs) is usually hereditary and may have more dystonic features than the adult onset disorder.

Causes

The underlying cause of most cases of PD is not known and the term idiopathic PD is used to describe the disease. Many of the clinical features of PD can result from a variety of other conditions including vascular disease, drugs, neurodegeneration and rarely encephalitis. When this happens the condition is called parkinsonism rather than PD.

Pathophysiology

The classic features of PD are a result of degeneration of dopamine secreting substantia nigra neurones which project from the brainstem via the striatal neurones to the basal ganglia. This leads to a loss of the characteristic black pigment and the remaining dopamine secreting cells may show Lewy inclusion bodies. Clinical disease starts when the substantia nigra cell loss is >50% and striatal dopamine levels are reduced by >80%. Recent studies have shown however that the pathology in PD is more widespread and occurring much earlier than originally believed.

This chapter is concerned with the main protozoal and helminthic infections affecting the nervous system in Africa. These include cerebral malaria, toxoplasmosis, and human African trypanosomiasis (HAT), neurocysticercosis, schistosomiasis and hydatid disease. The student should aim to be familiar with these, including life cycles, clinical presentations, diagnosis, management and prevention.

CEREBRAL MALARIA

Cerebral malaria is a severe neurological disease of the brain that is caused by Plasmodium falciparum and is characterized by fever, altered level of consciousness and laboratory evidence of malaria infection. The research definition of cerebral malaria is unrousable coma, (Glasgow coma scale ≤8 or Blantyre coma scale for young children ≤2 (Table 7.2) in the presence of a peripheral parasitaemia after other causes of coma have been excluded.

Epidemiology

Each year there are over 300 million new cases of malaria in Africa resulting in over 1 million deaths there, occurring mostly but not exclusively in children. Cerebral malaria is one of the most important complications. It is invariably fatal without treatment and each year there are over half a million new cases of cerebral malaria in Africa. Most cases occur in non immune children (<5 yrs) and the incidence declines progressively as children become older. Cerebral malaria also occurs in adults but much less frequently. The mortality rate in treated cerebral malaria in children is 15-20% and 10-15% in adults. Recent reports and clinical experience in Africa suggest that the overall burden of severe malaria is decreasing significantly there.

Pathophysiology of cerebral malaria

The mechanism of brain injury in cerebral malaria is not fully understood. The main theories involve parasite sequestration, endothelial dysfunction and injury with cytokine release and blood brain barrier dysfunction. The brain at post mortem in cerebral malaria is typically congested and darkened in colour (Fig 7.1). The histopathology shows many parasitized red blood cells (RBCs) sequestered in the capillaries and small blood vessels particularly in the grey matter and petechial perivascular ring haemorrhages in white matter (Fig 7.1). The sequestration is attributed to cytoadherence or the sticking of parasitized RBCs to vascular endothelium and to rosetting; the sticking of unparasitized RBCs around a parasitized RBC, which in turn may lead to congestion of the capillaries. These findings have led to the mechanical theory of decreased microcirculation or blocked capillaries being a main mechanism.

Introduction

Neurology relies on the fundamental skills of history taking and physical examination. The aim of this section is to help the medical student to learn the basic clinical skills necessary to carry out a neurological history and examination and interpret the findings. Most students find neurology difficult to remember and in particular what to do, how to do it and what it all means. The history is the most important part of neurological evaluation because it is a guide to the underlying disease and also determines which part of the examination needs to be focused on. Indeed many neurological diseases like migraine have symptoms but no abnormal signs. The neurological examination determines abnormal neurological findings and helps to localize the site of the disease (Chapters 2 & 12). The history, examination and localization all together help to determine which disease has occurred at that site. The necessary competence required to carry out these tasks is formed by a combination of knowledge, skills and experience. Neurological knowledge is mostly self learned while clinical skills are taught at the bedside and experience gained over time. The nervous system by its nature is complex but its assessment can be learned with patience, plenty of practice and time.

HISTORY TAKING

Introduction

The history is the most important part of the neurological assessment. The student should aim to be a good listener showing interest and sympathy as the patient's story unfolds. It is important to get the patient's trust and confidence. First introduce yourself to the patient, explain who you are and ask permission to take a history and to carry out an examination. Find out the patient's name, age, address, occupation. Determine handedness by asking which hand do you write with or use more often. Some clinical findings are apparent to the examiner during history taking; these include general state of health and obvious neurological deficits and disabilities. If there is alteration in the level of consciousness or the patient is unable to give a history then it may be necessary to obtain a history and witnessed account from a relative or friend before proceeding directly to neurological examination. The patient's history reveals his personality, intelligence, memory and speech and his body language his attitude and mood.

Introduction

Epilepsy is a predisposition to recurrent unprovoked seizures. Seizures are caused by attacks of sudden, excessive, abnormal electrical discharges arising mainly from the neurones in the cortex of the brain. The site, spread and pattern of electrical discharges determine the clinical features of epilepsy. The seizures may range from a brief awareness of sensation lasting only seconds to a sudden loss of consciousness associated with involuntary stiffening and jerking body movements. The latter is termed generalized tonic-clonic epilepsy and historically was called grand mal. Epilepsy is the most common community based major neurological disorder and the individual case history and description of the seizure are crucial to the diagnosis of epilepsy. This chapter outlines the main epilepsy syndromes, their classification, causes, clinical presentation diagnosis and management. The student should aim for an overall understanding of epilepsy and in particular its burden, diagnosis, management and treatment.

EPILEPSY SYNDROMES

Epilepsy is classified according to cause and clinical seizure type. Idiopathic epilepsy (60-70%) occurs where no known cause is found or suspected and many of these are most likely genetic in origin. Symptomatic epilepsy (30-40%) occurs when there is an underlying structural abnormality in the cerebral cortex such as a scar or tumour or another condition predisposing to seizures. Seizures in epilepsy may be classified according to their clinical presentation and their site of electrical origin in the brain (Table 4.1). If seizures arise focally from one site within the brain these are termed as the partial onset seizures. These can present with motor, sensory, autonomic and psychological symptoms. If the electrical discharge remains focal and consciousness is fully retained, these are classified as simple partial seizures. If the electric discharge arises focally and consciousness is altered, these are classified as complex partial seizures. If the electrical discharge arises focally and spreads to involve the rest of the entire cerebral cortex, this results in a generalized tonic-clonic seizure. These are classified as secondary generalized tonic-clonic seizures (grand mal) and are the most common type of seizure disorder (70%). Seizures may also arise from electrical discharges deep within the brain spreading equally rapidly to all parts of the cortex at the same time. These are termed as generalized onset seizures (30%).

Neurological disorders are a frequent manifestation of HIV infection in Africa. At least a fifth of infected persons will present with a major neurological illness either as the first clinical manifestation of HIV or occurring during the course of symptomatic HIV disease. The proportion of patients with clinical evidence of neurological dysfunction and have abnormal neurological findings is however much higher at 40-70%. At post mortem examination, over 90% of AIDS cases have pathological changes in their nervous system. Neurological disorders affect all parts of the nervous system including the brain, spinal cord, peripheral nerves, muscle and eye. This chapter outlines the main neurological illnesses arising from HIV infection. After reading the chapter the student should aim to understand the main mechanisms, clinical presentations, diagnosis and management of these illnesses.

INTRODUCTION

Neurological disorders in HIV infection are caused by three main processes: loss of cellmediated immunity, direct HIV infection, and inflammation/autoimmunity. Adverse effects of drugs used to treat HIV and its co infections are also a cause.

Disorders related to loss in immunity are caused by opportunistic processes (OP), mostly infections and occasionally neoplasms. These occur mostly but not exclusively when the CD4 count is <200 cells/cm3. The main opportunistic infections (OI) are cryptococcosis, toxoplasmosis and tuberculosis (Chapters 6 & 7) and main opportunistic neoplasm is cerebral lymphoma. The main neurological presentations occurring as a result of those processes are meningitis, focal neurological disorder (FND) and altered level of consciousness or coma depending on the cause and CNS site involved.

Neurological disorders also arise from direct HIV infection of the nervous system and muscle. These include HIV-associated dementia (HAD), distal sensory neuropathy (DSN), vacuolar myelopathy, retinopathy and myopathy. These also occur mostly during the later stages of HIV infection when CD4 count is <100 cells/cm3.

Other neurological disorders that may occur throughout the course of HIV infection include herpes zoster, Bell's palsy, Guillain-Barre Syndrome (GBS) and polymyositis. These by contrast occur mostly during the asymptomatic stage when immunity is still relatively intact with CD4 counts typically >200 cells/cm3. GBS and polymyositis are caused by inflammation and autoimmunity. The general characteristics of the main HIV related neurological illnesses are summarized below in Table 8.1.