A significant and oft-invoked barrier to effective health care in resource-poor settings is the lack of medical personnel. In what is termed the brain drain, many physicians and nurses emigrate from their home countries to pursue opportunities abroad, leaving behind health systems that are understaffed and ill-equipped to deal with the epidemic diseases that ravage local populations. The WHO recommends a minimum of 20 physicians and 100 nurses per 100,000 persons, but recent reports from that organization and others confirm that many countries, especially in sub-Saharan Africa, fall far short of those target numbers. More than half of these countries register fewer than 10 physicians per 100,000 population. In contrast, the United States and Cuba register 279 and 596 doctors per 100,000 population, respectively. Similarly, the majority of sub-Saharan African countries do not have even half of the WHO-recommended minimum number of nurses. In addition to these appalling national aggregates, further inequalities in health care staffing exist within countries. Rural-urban disparities in health care personnel mirror disparities of both wealth and health. In 1992, the poorest districts in southern Africa reported 5.5 doctors, 188.1 nurses, and 0.5 pharmacists per 100,000 population. The same survey found, in the richest districts, 35.6 doctors, 375.3 nurses, and 5.4 pharmacists per 100,000 population. Nearly 90% of Malawi's population is rural, but >95% of clinical officers were at urban facilities, and 47% of nurses were at tertiary care facilities. Even community health workers, trained to provide first-line services to rural populations, often transfer to urban districts. In 1989 in Kenya, for example, there were only 138 health workers per 100,000 persons in the rural North Eastern Province, whereas there were 688 per 100,000 in Nairobi.
In addition to inter- and intranational transfer of personnel, the AIDS epidemic contributes to personnel shortages across Africa. Although data on the prevalence of HIV infection among health professionals are scarce, the available numbers suggest substantial and adverse impacts on an already-overburdened health sector. In 1999, it was estimated that 17–32% of health care workers in Botswana had HIV disease, and this number is expected to increase in the coming years. A recent study that examined the fates of a small cohort of Ugandan physicians found that at least 22 of the 77 doctors who graduated from Makerere University Medical School in 1984 had died by 2004—most, presumably, of AIDS. Similar numbers have been registered in South Africa, where a small study by the Human Sciences Research Council found an HIV seroprevalence among health professionals similar to that among the general population—in this case, 15.7% of all health care workers surveyed. The shortage of medical personnel in the areas hardest hit by HIV has profound implications for prevention and treatment efforts in these regions. The cycle of health-sector impoverishment, brain drain, and lack of personnel to fill positions when they are available conspires against ambitious programs to bring ART to persons living with both AIDS and poverty. The president of Botswana recently declared that one of his country's main obstacles to rapid expansion of HIV/AIDS treatment is "a dearth of doctors, nurses, pharmacists, and other health workers."3 In South Africa, the departure of nearly 600 pharmacists in 2001, coupled with standing vacancies for 32,000 nurses, has put continued strain on that relatively affluent country's ability to respond to calls for expanded treatment programs. In Malawi, only 28% of established nursing posts are filled. Furthermore, the education of medical trainees is jeopardized as the ranks of the health and academic communities continue to shrink as a result of migration or disease. The long-term implications are sobering.
A proper biosocial analysis of the brain drain reminds us that the flight of health personnel—almost always, as most reviews suggest, from poor to less-poor regions—is not simply a question of desire for more equitable remuneration. Epidemiologic trends and access to the tools of the trade are also relevant, as are working conditions in general. In many settings now losing skilled health personnel, the advent of HIV has led to a sharp rise in TB incidence; in the eyes of health care providers, other opportunistic infections have also become insuperable challenges. Together, these forces have conspired to render the provision of proper care impossible, as the comments of a Kenyan medical resident suggest: "Regarding HIV/AIDS, it is impossible to go home and forget about it. Even the simplest opportunistic infections we have no drugs for. Even if we do, there is only enough for a short course. It is impossible to forget about it. . . . Just because of the numbers, I am afraid of going to the floors. It is a nightmare thinking of going to see the patients. You are afraid of the risk of infection, diarrhea, urine, vomit, blood. . . . It is frightening to think about returning."4 Another resident noted, "Before training we thought of doctors as supermen. . . . [Now] we are only mortuary attendants."5 Nurses and other providers are, of course, similarly affected.
Given the difficult conditions under which these health care personnel work, is it any surprise when the U.S. government's appointed Global AIDS Coordinator notes that there are more Ethiopian physicians practicing in Chicago than in all of Ethiopia? In Zambia, only 50 of the 600 doctors trained since the country's independence in 1964 remain in their home country. Nor is it surprising that a 1999 survey of medical students in Ghana in their final year of training revealed that 40 of 43 students planned to leave the country upon graduation. When providing care for the sick becomes a nightmare for those at the beginning of clinical training, physician burn-out soon follows among those who carry on in settings of impoverishment. In the public-sector institutions put in place to care for the poorest people, the confluence of epidemic disease, lack of resources with which to respond, and unrealistically high user fees has led to widespread burn-out among health workers. Patients and their families are those who pay most dearly for provider burn-out, just as they bear the burden of disease and—with the introduction of user fees—much of the cost of responding, however inadequately, to new epidemics and persistent plagues.
3Dugger C: Botswana's brain drain cripples war on AIDS. New York Times A10 (13 November 2003).
4Raviola G et al: HIV, disease plague, demoralization, and "burnout": Resident experience of the medical profession in Nairobi, Kenya. Cult Med Psychiatry 26:55, 2002.
5Ibid.
Thursday, November 20, 2008
Health Systems and the "Brain Drain"
Sunday, November 2, 2008
physical examination for Multi-infarct Dementia
The physical examination should be focused on the cardiovascular system and neurologic localizing signs.
- The temporal arteries may show decreased pulsatility, local tenderness, and thickening associated with giant cell arteritis.
- Funduscopic examination provides important information regarding end-organ effects of hypertension and diabetes mellitus.
- Cardiac auscultation may detect rhythmic and valvular abnormalities.
- Low scores on a standardized instrument (eg, Mini Mental Status Examination, Short Blessed questionnaire) can provide corroborating evidence of a cognitive disturbance.
- Spasticity, hemiparesis, visual field defects, pseudobulbar palsy, and extrapyramidal signs confirm focal pathology.
Multi-infarct Dementia
Multi-infarct Dementia
Background
Dementia is a common neurologic syndrome with significant impact on the mortality and morbidity of elderly persons with the most common forms being Alzheimer disease (AD) and vascular dementia (VaD). VaD is a heterogeneous entity with a large clinicopathological spectrum that has been classically linked to cortical and subcortical ischemic changes resulting from systemic, cardiac, or local large- or small-vessel disease occlusion. Thus, the diagnosis of VaD is usually made on the basis of clinical, neuroimaging, or neuropathological evidence of cerebral ischemia in the presence of progressive cognitive decline. On the other hand, vascular pathology often coexists with AD, and this poses an additional diagnostic challenge. This has led to the existence of the diagnostic term of mixed dementia.
This diagnosis is made in the presence of neuropathologic hallmarks of AD such as accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles, and cerebral amyloid angiopathy (CAA) as well as evidence of significant ischemic events.
The frequent coexistence of AD and VaD pathologies in postmortem studies has led many to suggest that these two entities are mechanistically related. Further evidence for this comes from the significant overlap in risk factors for AD and vascular disease such as hypertension, diabetes, and apoE4 genotype. Furthermore, cerebral hypoperfusion as detected by positron emission tomography (PET) has been demonstrated in early stages of AD. Also CAA, which is prevalent in AD brains, could further alter cerebral hemodynamics. Despite these observations, the mechanisms of vascular-AD interactions are poorly understood, and the question remains as to whether these two entities interact in a synergistic fashion.
Pathophysiology
Vascular dementia results from brain injury caused by stroke and cerebral ischemia.
Single ischemic or thromboembolic infarcts occurring in strategic areas of the dominant hemisphere (eg, angular gyri, mediodorsal thalamus, anterior thalamus) may cause a dementialike syndrome without the involvement of large volumes of cerebral matter. In general, volume of tissue loss is a poor predictor of the severity of the cognitive impairment.
More commonly, progressive cognitive deficits and dementia can result from multiple temporally staggered small cerebral infarcts. Frontal subcortical regions supplied by small penetrating arterioles may be especially prone to degenerative changes in patients with poorly controlled hypertension, diabetes mellitus, or both.
A less common cause of VaD is global hypoxic-ischemic injury (eg, following cardiac arrest). Irreversible cognitive impairment is frequently observed following coronary bypass surgery.
Whether chronic cerebral ischemia associated with carotid artery stenosis (CAS) may alter cognitive function has not been conclusively demonstrated and remains a controversial concept. Neuropsychometric evaluation of patients undergoing carotid endarterectomy has not conclusively shown cognitive impairment or reductions in the probability of developing dementia in the long term.
An ill-understood form of VaD is Binswanger encephalopathy. Postmortem, myelin loss is observed and is most prominent in the hemispheric deep white matter. Axonal drop out is also observed with little or no signs of inflammation. Neuroimaging shows decreased white matter density on CT scanning and decreased white matter intensity on T1-weighed MRI. Frequently, but not invariably, lacunar strokes are also observed.
Dementia associated with cerebrovascular disease is also observed in a rare genetic condition, ie, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Affected patients often present with migraines with aura. Recurrent strokes start when the patients are aged 30-50 years. Multiple lacunar infarcts, mainly in the frontal white matter and basal ganglia, lead to progressive cognitive decline and finally dementia. However, cognitive decline is thought to begin even before strokes occur, suggesting that chronic cerebral hypoperfusion in the absence of overt stroke might be sufficient to cause significant neuronal circuit disruption.
Lastly, cognitive decline has been reported in association with several other vasculopathies such as temporal arteritis, polyarteritis nodosa, primary cerebral angiopathy, lupus erythematosus, and moyamoya disease.
Multi-infarct Dementia
Multi-infarct Dementia
Background
Dementia is a common neurologic syndrome with significant impact on the mortality and morbidity of elderly persons with the most common forms being Alzheimer disease (AD) and vascular dementia (VaD). VaD is a heterogeneous entity with a large clinicopathological spectrum that has been classically linked to cortical and subcortical ischemic changes resulting from systemic, cardiac, or local large- or small-vessel disease occlusion. Thus, the diagnosis of VaD is usually made on the basis of clinical, neuroimaging, or neuropathological evidence of cerebral ischemia in the presence of progressive cognitive decline. On the other hand, vascular pathology often coexists with AD, and this poses an additional diagnostic challenge. This has led to the existence of the diagnostic term of mixed dementia.
This diagnosis is made in the presence of neuropathologic hallmarks of AD such as accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles, and cerebral amyloid angiopathy (CAA) as well as evidence of significant ischemic events.
The frequent coexistence of AD and VaD pathologies in postmortem studies has led many to suggest that these two entities are mechanistically related. Further evidence for this comes from the significant overlap in risk factors for AD and vascular disease such as hypertension, diabetes, and apoE4 genotype. Furthermore, cerebral hypoperfusion as detected by positron emission tomography (PET) has been demonstrated in early stages of AD. Also CAA, which is prevalent in AD brains, could further alter cerebral hemodynamics. Despite these observations, the mechanisms of vascular-AD interactions are poorly understood, and the question remains as to whether these two entities interact in a synergistic fashion.
Pathophysiology
Vascular dementia results from brain injury caused by stroke and cerebral ischemia.
Single ischemic or thromboembolic infarcts occurring in strategic areas of the dominant hemisphere (eg, angular gyri, mediodorsal thalamus, anterior thalamus) may cause a dementialike syndrome without the involvement of large volumes of cerebral matter. In general, volume of tissue loss is a poor predictor of the severity of the cognitive impairment.
More commonly, progressive cognitive deficits and dementia can result from multiple temporally staggered small cerebral infarcts. Frontal subcortical regions supplied by small penetrating arterioles may be especially prone to degenerative changes in patients with poorly controlled hypertension, diabetes mellitus, or both.
A less common cause of VaD is global hypoxic-ischemic injury (eg, following cardiac arrest). Irreversible cognitive impairment is frequently observed following coronary bypass surgery.
Whether chronic cerebral ischemia associated with carotid artery stenosis (CAS) may alter cognitive function has not been conclusively demonstrated and remains a controversial concept. Neuropsychometric evaluation of patients undergoing carotid endarterectomy has not conclusively shown cognitive impairment or reductions in the probability of developing dementia in the long term.
An ill-understood form of VaD is Binswanger encephalopathy. Postmortem, myelin loss is observed and is most prominent in the hemispheric deep white matter. Axonal drop out is also observed with little or no signs of inflammation. Neuroimaging shows decreased white matter density on CT scanning and decreased white matter intensity on T1-weighed MRI. Frequently, but not invariably, lacunar strokes are also observed.
Dementia associated with cerebrovascular disease is also observed in a rare genetic condition, ie, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Affected patients often present with migraines with aura. Recurrent strokes start when the patients are aged 30-50 years. Multiple lacunar infarcts, mainly in the frontal white matter and basal ganglia, lead to progressive cognitive decline and finally dementia. However, cognitive decline is thought to begin even before strokes occur, suggesting that chronic cerebral hypoperfusion in the absence of overt stroke might be sufficient to cause significant neuronal circuit disruption.
Lastly, cognitive decline has been reported in association with several other vasculopathies such as temporal arteritis, polyarteritis nodosa, primary cerebral angiopathy, lupus erythematosus, and moyamoya disease.
TREATMENT for apraxia
TREATMENT for apraxia
Medical Care
Diagnosis is the most important aspect of apraxia. Consequences include diminished ability of the patient to live independently; patients therefore may require additional rehabilitation or skilled nursing care. Education of the patient's family is obviously a key part of evaluation.
Patients with childhood apraxia of speech are at risk for persistent reading and spelling disorder in addition to their spoken communication difficulties. A potential benefit has been shown of an integrated phonological awareness approach to improve speech, phonological awareness, and decoding ability simultaneously.
Patients may not request physical or occupational therapy because they may be unaware of their deficits. Such therapy is important, as part of both assessment and treatment of the patient.
Medicines are not known to be effective for the treatment of ideomotor apraxia. Levodopa-carbidopa (Sinemet) and dopamine agonist medications (eg, ropinirole [Requip], pramipexole [Mirapex]), typically are not effective for corticobasal ganglionic degeneration, although they are tried frequently. Antispasticity treatments, such as baclofen (Lioresal), tizanidine (Zanaflex), and botulinum toxin (Myobloc), can be tried for patients with a clenched fist due to a useless limb. Cholinesterase inhibitors, such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) may be used for progressive dementia syndromes, especially Alzheimer disease.
Diet
Patients with apraxia may have difficulty knowing how or what to eat. If a patient is losing weight or nutritional deficiencies are suspected, nutritional supplements or dietary assistance might be provided.
Activity
Patients with certain types of dementia may have a high risk of falling. Patients with corticobasal ganglionic degeneration or progressive supranuclear palsy may have a high fall rate relatively early in the disease, whereas patients with Alzheimer are more likely to fall in the middle to late stages. Patients with a useless upper limb may develop a clenched painful fist that severely limits activity.
Pathophysiology of Apraxia
Pathophysiology of Apraxia
Apraxia is a syndrome reflecting motor system dysfunction at the cortical level, exclusive of primary motor cortex. In planning movements, previously learned, stored complex representations of skilled movements are used. These 3-dimensional, supramodal codes, also called representations or movement formulae, are stored in the inferior parietal lobule of the left hemisphere. Diseases that involve this part of the brain, including strokes, dementias, and tumors, can cause loss of knowledge about how to perform skilled movements.
Apraxia can occur with lesions in other locations as well. Information contained in praxis representations is transcoded into innervatory patterns by the premotor cortices, including the supplementary motor area (SMA) and possibly the convexity of the premotor cortex; the information is then transmitted to the primary motor cortex and a movement is performed. Lesions of the SMA or other premotor cortices also can cause apraxia; in this case, knowledge about movement is still present, but the ability to perform movement is absent.
Apraxia also occurs with lesions of the corpus callosum, such as tumors or anterior cerebral artery strokes. Although the corpus callosum is not known to be involved directly in the performance of skilled movements, it contains crossing fibers from the right hemisphere to the premotor cortex. This type of apraxia represents a classic disconnection syndrome; patients with callosal apraxia typically are apractic only with the left hand.
Apraxia and Related Syndromes
Apraxia and Related Syndromes
Apraxia is one of the most important and least understood major behavioral neurology syndromes. It is one of the best localizing signs of the mental status examination and also predicts disability in patients with stroke or dementia (unlike aphasia). Patients with apraxia cannot use tools; therefore, they are unlikely to perform activities of daily living well. Patients with aphasia, without coexisting apraxia, can live independently, take the bus or subway, and lead a relatively normal life; a patient with significant limb apraxia is likely to remain dependent.
Heilman defined apraxia in negative terms, "Apraxia is defined as a disorder of skilled movement not caused by weakness, akinesia, deafferentation, abnormal tone or posture, movement disorders such as tremors or chorea, intellectual deterioration, poor comprehension, or uncooperativeness."1 To simplify matters, apraxia can be considered a form of a motor agnosia. Patients are not paretic but have lost information about how to perform skilled movements.
There is no consensus on how to divide and organize the many different syndromes known as apraxias. Authors have divided apraxias based on the following:
- Body part affected (eg, limb apraxia or buccofacial apraxia)
- Dysfunctional sensory area (left inferior parietal) or motor areas (left premotor and left supplementary motor)
- If use of tools is affected (transitive vs intransitive)
- If knowledge about the use of tools is preserved (conceptual)
- Deficits in pantomiming tool use and gesture (ideomotor)
The term apraxia is used to describe a variety of syndromes, including the following, which are not considered true apraxias by some.
- Dressing apraxia - Usually associated with right parietal lesions and part of a neglect syndrome
- Constructional apraxia - Inability to copy 2-dimensional drawings or 3-dimensional assemblies (may be associated with right or left
- parietal and left frontal among other brain regions)
- Gait apraxia - Part of the triad of symptoms of normal pressure hydrocephalus
- Gaze apraxia - Part of Balint syndrome
- Apraxia of eyelid opening
- Magnetic apraxia
FOLLOW-UP of Dementia in Motor Neuron Disease
FOLLOW-UP of Dementia in Motor Neuron Disease
Deterrence/Prevention
No effective methods exist.
Complications
Progressive bulbar palsy results in dysphagia, the risk of aspiration pneumonia, and mutism.
Muscular wasting and weakness may occur.
Parkinsonism may develop in some patients.
Dyspnea and hypoxic encephalopathy may be related positionally and can interfere with reclining for sleep.
Prognosis
Clinical signs of MND follow or accompany the onset of dementia.
MND is responsible for death, which usually occurs within 3 years of onset.
Patient Education
For excellent patient education resources, visit eMedicine's Dementia Center. Also, see eMedicine's patient education articles Dementia Overview, Dementia Medication Overview, and Dementia in Amyotrophic Lateral Sclerosis.
MEDICATION of Dementia in Motor Neuron Disease
MEDICATION of Dementia in Motor Neuron Disease
No specific treatment is available for FTD/MND. Treatments for MND, such as riluzole and gabapentin, do not appear to affect the course of the dementia-inducing illness. Riluzole is currently the only licensed medication for MND. Available data from therapeutic trials in MND do not show beneficial cognitive effects, although there are no specific contraindications in this context. Gabapentin has been studied in trials as a disease-modifying agent in patients with MND but does not demonstrate specific cognitive-enhancing properties.
Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) are used to correct the cholinergic effect associated with Alzheimer disease. Although not studied specifically in FTD, anecdotal reports suggest they may increase irritability in patients with FTD.
FTD patients with profound presynaptic serotonergic deficits and behavioral disturbances may respond to selective serotonin reuptake inhibitors.
Selective dopamine-blockers, such as olanzapine, may be useful in agitated patients; monitor for side effects such as extrapyramidal syndromes. While plausible, it is not certain that treatment strategies for FTD apply to FTD/MND. Current treatments mainly are supportive and directed toward the features of MND.
TREATMENT of Dementia in Motor Neuron Disease
TREATMENT of Dementia in Motor Neuron Disease
Medical Care
Direct prehospital care to aspects of MND that accompany the dementia.
Evaluate and treat sialorrhea, impaired breathing, swallowing, and mobility.
Consider neuroprotective agents (eg, riluzole, gabapentin) or nutritional supplements (eg, creatine) to preserve muscle bulk, but note that their efficacy in FTD/MND is even more uncertain than in MND.
Surgical Care
There is no surgical treatment for FTD/MND.
Consider gastrostomy tube feeding for patients with severe bulbar symptoms, severe dysphagia, and relatively mild dementia and limb weakness.
Diet
Patients may develop bulbar palsy, necessitating parenteral nutrition or percutaneous gastrostomy. Prior to gastrostomy, mechanically soft diets can be tried.
Activity
Level of activity is dictated by progression of MND.
WORKUP of Dementia in Motor Neuron Disease
WORKUP of Dementia in Motor Neuron Disease
Lab Studies
Obtain typical blood studies, thyroid function tests, vitamin B12 and folate levels, and Venereal Disease Research Laboratory test. Refer to Amyotrophic Lateral Sclerosis for a full listing of the MND workup.
Imaging Studies
Computed tomography (CT) scan may show mild, generalized cerebral atrophy or asymmetric frontotemporal atrophy.
Because of greater resolution than CT, MRI studies may reveal selective frontal and anterior temporal atrophy that cannot be appreciated on CT.
Single photon emission computed tomography imaging often demonstrates reduced blood flow in an asymmetric, frontotemporal pattern.
A recent study reported that glucose hypometabolism on PET imaging in patients with dementia associated with motor neuron disease affected only the frontal lobes, sparing the temporal lobes. This is in contrast to frontotemporal dementia where glucose hypometabolism is seen in both frontal lobes and temporal lobes. In Alzheimer disease, PET scans may reveal glucose hypometabolism in the parietal and temporal regions bilaterally.
Other Tests
Electroencephalogram can remain normal even in later stages of dementia, but often mild dysrhythmic slowing occurs that is sometimes asymmetric.
Electromyography may demonstrate widespread denervation in limb muscles. Early in the disease, especially in predominantly bulbar onset patients, findings may not fulfill the Lambert or El Escorial criteria for MND.
Histologic Findings
Early in the disease, FTD/MND preferentially affects frontal and temporal lobes, the hypoglossal nucleus, and spinal motor neurons. Later and terminal stages reveal histologic evidence of widespread cortical involvement. In the frontal and temporal lobes, microscopic changes include loss of pyramidal cells, spongiform neuropil change, and astrocytic gliosis. Ubiquinated, tau-negative inclusions are present within the frontal cortex and the dentate gyrus of the hippocampus. Pick cells (inflated neurons) and Pick bodies (ubiquitin and tau-positive intracellular inclusions) are absent. Betz cells in the precentral gyrus usually are affected.
In approximately 50% of patients, neuronal loss and pigmentary incontinence in the substantia nigra and other pigmented brainstem neurons occurs, even in patients without clinically overt parkinsonism. There can be marked hypoglossal and spinal motor neuron degeneration (although this is not essential for patients to progress to an anarthric state) and ubiquinated tau-negative inclusions in the spinal neurons.
CLINICAL of Dementia in Motor Neuron Disease
CLINICAL of Dementia in Motor Neuron Disease
History
- FTD/MND usually presents as a change in personality with deterioration in social conduct.
- Initial behavioral changes vary but include abulia, apathy, and reduced spontaneity and/or initiation.
- Some patients become strikingly disinhibited, overactive, and frankly inappropriate with emotional lability.
- With disease progression, even those patients manifesting disinhibition and restlessness become increasingly apathetic.
- Stereotypic behavior and repetitive rituals of hoarding, dressing, wandering, and toileting can be observed.
- Patients may overeat, exhibit hyperoral tendencies, and develop food fads (although this is more exceptional); some patients may hold food in their mouth for prolonged periods without swallowing.
- Dynamic spontaneous speech output progressively declines, resulting in anarthria and mutism. Visuospatial skills are relatively spared throughout illness, but there is significant memory impairment.
- A subset of patients presents with rapidly progressive aphasia.
- Despite progression to anarthria, autopsy studies show that anarthria can occur in the absence of significant hypoglossal nucleus involvement.
- Memory also is impaired, but this is not as distinguishing as the frontal lobe or language features.
- Posterior cortical functions (eg, visuospatial skills) are preserved and/or spared until the preterminal stages.
- The clinical pattern reflects the topographic pattern of atrophy, often visible radiographically, with asymmetric frontotemporal atrophy.
- If asymmetrically worse in the left (language-dominant) hemisphere, aphasia is a likely and prominent clinical feature.
- Throughout the course of the disease, signs and symptoms of MND also progress.
- Cognitive changes often precede signs of MND.
- Limb weakness and dysphagia eventually become disabling, although some patients have a primarily bulbar pattern of weakness with relative sparing of limb strength.
- Recently, consensus clinical criteria detailing core and supportive features for FTD syndromes were published.
Physical
- Patients usually perform poorly on tests of frontal lobe function (ie, Wisconsin card sorting, picture sequencing, verbal fluency tests). Memory is impaired, but less consistently in the mild stages.
- Clinical signs of MND usually follow or accompany dementia onset. MND signs include bulbar weakness with dysarthria and dysphagia, limb weakness, muscle wasting and fasciculations, and, of greatest concern, dyspnea.
- Akinesia and rigidity are uncommon in this disorder but more common in patients with a longer interval between onset of dementia and neurologic signs (more than 24 mo in a Japanese series). This may reflect, in part, the variable involvement of the substantia nigra and other pigmented brainstem nuclei that are observed in roughly 50% of patients at autopsy. This, in turn, may vary between populations (more common in Chamorro Indians).
Causes
- Worldwide, FTD/MND is sporadic with unknown etiology.
- A minority of patients has a family history, but this overlap syndrome may be related to other neurodegenerative overlap syndromes that include variable degrees of dementia, MND, and parkinsonism.
- Familial cases of this type are linked to a mutated region of chromosome 17, which contains the tau gene. It is possible that a similar genetic association will be found for FTD/MND.
INTRODUCTION of Dementia in Motor Neuron Disease
INTRODUCTION of Dementia in Motor Neuron Disease
Background
Most patients with motor neuron disease (MND) are free of cognitive impairment, but there is growing evidence of an association between MND and frontal lobe or frontotemporal dementia (FTD). Some propose that frontotemporal lobe dementia with motor neuron disease (FTD/MND) is nosologically distinct; others suggest that it is part of a spectrum of diseases encompassing classic MND at one end and FTD at the other.
Pathophysiology
Pyramidal cell loss in frontal and temporal lobes and degeneration of motor neurons in the hypoglossal nucleus and spinal motor neurons characterize FTD/MND. Pyramidal neurons in the premotor cortex usually are preserved. Signs and symptoms reflect frontal and temporal lobe dysfunction with lower motor neuron-type weakness, muscle atrophy, and fasciculations.
Frequency
United States
Frontal lobe dementia is the second or third most common type of degenerative dementia in autopsy series. The precise frequency of the subgroup of FTD patients with FTD/MND in autopsy or population studies is unknown (but rare).
International
In a Scandinavian autopsy series, dementia was reported in 2-6% of patients with MND. The relative frequency of FTD/MND in all patients with dementia appears similar in the United States and Japan. Certain populations (eg, Chamorro Indians of Guam, indigenous residents of the Kii peninsula) have a disproportionately higher incidence and prevalence of overlap degenerative syndromes (MND, dementia, parkinsonism).
Mortality/Morbidity
Progressive dementia with symptoms of executive dysfunction, personality change, and motor weakness leads to severe morbidity.
Death usually occurs within 3 years of onset from inanition, pulmonary failure, and aspiration.
Patients with FTD/MND generally follow a more rapid course than patients with either FTD or MND alone. They are more likely to have a bulbar form of MND, which may help explain its more aggressive course.
Race
FTD/MND has been described in patients of Asian, European, and African descent. No data are available about incidence and prevalence among racial groups.
Sex
Men appear to be affected slightly more frequently than women, but this difference may not be significant.
Age
The mean age of onset in sporadic cases varies among series but overall is 55-65 years. Familial cases tend to be younger.
TREATMENT of Minimal Cognitive Impairment
TREATMENT of Minimal Cognitive Impairment
Medical Care
At present, no treatment for MCI exists. Several trials are currently underway to determine whether cholinesterase inhibitors, anti-inflammatory agents, and antioxidants may be beneficial in MCI. Smaller scale studies suggest that at least some cholinesterase inhibitors may improve the memory loss (Freo, 2001), although larger scale studies are necessary to ascertain this more rigorously. Unfortunately, results presented so far with donepezil have been disappointing, but the results of a large-scale trial with rivastigmine have not been released yet.
A practice parameter recommendation by the American Academy of Neurology states that patients with MCI should be identified and monitored because of their increased risk for AD and, to a lesser extent, other dementing conditions. Obviously, correcting (to the extent possible) any sensory and motor manifestations compounding the cognitive symptoms is important to minimize their impact on MCI.
Activity
Because physical, social, and mental activity are often recommended for patients with AD and MCI often heralds AD, many experts have thought that mentally challenging activities, such as crossword puzzles and "brain teasers" may be helpful in MCI. While definitive proof of the efficacy of these exercises is unavailable at the time of this writing, recommending them to patients with MCI seems advisable. Keep such exercises within reasonable levels of difficulty for the patient. Exercises should preferably be interactive rather than passive, and they should also be administered in a fashion that does not cause excessive frustration. Social isolation can be minimized through referral to senior community centers or a day treatment program. Cognitive retraining/rehabilitative strategies offer considerable promise in MCI (D. Loewenstein, PhD, oral communication, March 2005) and are therefore being explored.
WORKUP of Minimal Cognitive Impairment
WORKUP of Minimal Cognitive Impairment
Lab Studies
No specific laboratory studies are indicated for MCI. Most practitioners perform at least a basic workup to rule out treatable conditions that may cause dementia, such as thyroid disease, cobalamin deficiency, and lues. These are not mandatory, however. A search for biological markers of MCI that may help distinguish among the many conditions that lead from this syndrome to full-blown dementia is ongoing. However, no unanimous agreement exists as of yet, and potentially useful markers such as functional and structural abnormalities found on imaging studies (eg, hippocampal atrophy, cerebral hypoperfusion) and putative biochemical markers (eg, apolipoprotein E epsilon 4 allele) remain controversial.
Imaging Studies
Brain imaging with computed tomography scanning or magnetic resonance imaging (preferably) is often performed in patients with MCI. No practice parameters have been recommended in this regard. However, findings indicate that hippocampal atrophy may correlate with MCI (Jack, 1999), although no established parameters exist to implement this correlation for the routine diagnosis and management of MCI.
Other Tests
Neuropsychological testing is probably useful in MCI, but this has not been conclusively demonstrated. While the value of such testing has been proven in AD and other dementias and is helpful to distinguish among dementing conditions, neither AD nor MCI can be diagnosed solely by using neuropsychological tests. The potential validity and utility of such tests will be determined in presently ongoing studies of large cohorts of patients with MCI. These ongoing studies will help define whether existing tests are useful in this context as well as in the design of new tests specifically adapted to patients with MCI.
CLINICAL of Minimal Cognitive Impairment
CLINICAL of Minimal Cognitive Impairment
History
Patients with MCI often present with vague and subjective symptoms of declining cognitive performance, which may be difficult to distinguish from the decline in such performance affecting healthy older individuals. The most common is said to be memory loss, consistent with the prevalent view that the amnestic form is the most common type of MCI. However, some authorities affirm that the most common form of MCI affects multiple spheres of cognition. Less common presentations include language disturbance (eg, word-finding difficulty), attentional deficit (eg, difficulty following or focusing on conversations), and deterioration in visuospatial skills (eg, disorientation in familiar surroundings in the absence of motor and sensory conditions that would account for the complaint).
Dissociating purely cognitive symptoms from those attributable to various degrees of sensory deprivation (eg, hearing loss, loss of visual acuity) that tend to coexist in the same patient population is often difficult and may be compounded by motor deficits that also beset the same individuals. In any case, the defining element of MCI as postulated by Petersen is a single sphere of slowly progressive cognitive impairment not attributable to motor or sensory deficits, to which other areas of involvement may eventually be added, before social or occupational impairment supervenes (because this marks the onset of dementia). Virtually nothing is known about the average duration of these manifestations before they are usually (if ever) brought to medical attention.
Physical
No feature of the general physical examination is characteristic of MCI. However, a physical examination should be performed as part of the general evaluation in an effort to determine whether conditions capable of causing MCI are present (eg, signs of thyroid disease, cobalamin deficiency, or venereal disease) and whether sensory and motor deficits are present, which could explain or compound the symptoms.
Causes
MCI is a heterogeneous condition due to numerous different causes, which may overlap in individual patients. In an attempt to distinguish among patient groups, emphasis is often placed on whether memory is involved or single nonmemory domains are involved instead. Thus, the most common form of MCI is thought to be amnesic MCI, in which the single domain affected is memory. A large percentage of these patients appear to progress to AD.
While accounts of MCI often revolve around the amnestic form because it is said to be the most common, other forms exist that are considerably less well characterized. Thus, a theoretically less common form of MCI is one in which multiple cognitive domains are affected; this is said to be associated with atypical variants of AD and dementia associated with cerebrovascular disease. Some epidemiological studies suggest that the multidomain form of MCI is more common than the amnestic form.
A third postulated type is one in which a single nonmemory domain is affected. Such a condition is believed to evolve frequently into frontotemporal dementia, Lewy body dementia, primary progressive aphasia, dementia in Parkinson disease, and other atypical variants of AD.
INTRODUCTION of Minimal Cognitive Impairment
INTRODUCTION of Minimal Cognitive Impairment
Background
Mild degrees of cognitive impairment, particularly when self-reported by patients, pose a substantial challenge to the clinician. The physician may be dealing with a patient with a mild or transient condition, a drug-induced adverse effect, or a depressive disorder; the patient may be in the early stages of a condition that will eventually lead to a dementia; or the complaint may be due to a psychological condition rather than an organic brain disorder. Because a variety of conditions may result in such a complaint, an individualized workup for such conditions and a consensus on a therapeutic approach should be sought.
In recent years, the term minimal cognitive impairment (MCI) is commonly used to refer to a stage of cognitive impairment (and specifically a subtype with memory loss [ie, amnestic MCI]) prior to attaining clinical criteria for dementia in Alzheimer disease (AD) and related disorders. However, no completely reliable means, other than long-term follow-up and eventual autopsy, exist to distinguish between patients experiencing MCI due to preclinical AD and patients experiencing MCI due to less frequently occurring conditions (Petersen, 2001). In this context, MCI is regarded as a high-risk condition that precedes AD in a large proportion of cases. It should be emphasized, however, that considerable controversy still exists considering the formulation of the concept of MCI and the practical implementation of the diagnosis. Furthermore, there is no consensus whatsoever as to treatments for this controversial condition.
In fact, the relatively recent formulation of MCI follows previous attempts to characterize cognitive decline associated with aging, including benign senescent forgetfulness, age-associated memory impairment, and age-associated cognitive decline (Crook, 1986; Kral, 1962; Levy, 1994). Therefore, this relatively new concept is perhaps best considered as a stage in the difficult process of understanding and characterizing mild defects in cognition that do not fit clearly within the scope of established neurological and psychiatric disorders.
In general, many of the previous terms imply extremes in a hypothetical process of normal aging as opposed to representing a precursor to pathological aging and dementia (eg, the "malignant" senescent forgetfulness [Kral, 1962]). Thus, in contrast with many previous terms, individuals with MCI have a condition that appears to some as different from normal aging in that long-term follow-up indicates that they tend to progress as a group to AD at an accelerated rate (Petersen, 1995; Petersen, 1999). Other terms with connotations similar to MCI include isolated memory impairment, incipient dementia, and dementia prodrome, although these latter terms are not nearly as widely accepted as MCI and they should not be considered as exact synonyms of MCI.
Pathophysiology
The pathophysiology of MCI is unknown. However, if one adopts the view that it most commonly results from AD, one hypothesis is that the disorder is associated with a gradual build-up of senile plaques and neurofibrillary tangles in areas of the cerebral cortex targeted by AD (entorhinal and perirhinal cortex) before the density of these lesions reaches the threshold necessary for the histopathologic diagnosis of AD (Morris, 2001). Similarly, the development of certain neurotransmitter deficiencies, and especially a cortical cholinergic deficiency, in the most common amnestic form of MCI is hypothesized. In the few studies undertaken to date, most patients with MCI have neuropathologic changes akin to AD, while a few individuals who are clinically similar do not have significant numbers of AD-like lesions (Mufson, 1999; Price, 1999; Troncoso, 1996). However, much larger numbers of patients with MCI must be studied before definitive statements can be made about the pathobiology of MCI.
Frequency in
United States
Annual prevalence estimates for MCI range from 17-34% among elderly populations (Barker, 1995; Larrabee, 1994; Petersen, 2001). However, note that only a relatively small amount of work has been conducted in the epidemiology of MCI because it is a comparatively recently characterized entity. In addition, most individuals evaluated in memory disorders facilities already meet the clinical criteria for dementia, justifying the perception that MCI is comparatively underrepresented in such populations.
Mortality/Morbidity
Amnestic MCI is said to progress to AD at a rate of 10-15% per year, as compared with healthy elderly individuals who develop AD at a rate of 1-2% per year. In addition, in a study from the Mayo Alzheimer's Disease Center, which monitored patients for over 10 years, the rate of conversion into AD was as high as 80% after 6 years of follow-up (Petersen, 1995). This is significant from the perspective that AD is often cast as the fourth leading cause of death in the United States.
Race
Virtually nothing is known about cultural and racial factors influencing the clinical manifestations of MCI.