A 72-year-old man presented with distal paresthesias, more pronounced in his hands than in his feet, unsteady gait, and frequent falls. His family noted some memory loss of unclear duration.
On examination, he was oriented to self and place but not to month or year. He immediately registered 3 items, but recalled only 1 item at 5 minutes with clues provided. Visual acuity was
poor. On motor examination, he had 4/5 lower extremity strength. His gait was broad based, spastic, and ataxic. Romberg sign was positive. He had loss of vibratory sense in the legs, absent
position sense in toes, and hyperesthesia to pinprick in distal extremities. Muscle stretch reflexes were normal. Babinski
signs were present. The patient's hematocrit was 29%, with a mean corpuscular volume of µm3. Vitamin B12 level was 34 (reference range, > 190pg/mL).
What is the diagnosis?
Subacute combined degeneration of spinal cord
Central pontine myelinosis
The symptoms of lead poisoning "plumbism" are non specific the diagnosis depends on an appreciation of the causative factors, a high index of suspicion, and the results of certain laboratory tests. The presence of lead lines at the metaphyses of long bones and basophilic stippling of red cells are too inconsistent to be relied on, but basophilic stippling of bone marrow normoblasts is uniformly increased. Impairment of heme synthesis, which is exquisitely sensitive to the toxic effects of lead, result in the increased excretion of urinary coproporphyrin (UCP) and of delta-aminolevulinic acid (ALA). These urinary indices and the lead concentration in serum bear an imperfect relationship to the clinical manifestations. ( The test for UCP, which is readily performed in the clinic and emergency department, a few milliliters of urine are acidified with acetic acid and shaken with an equal volume of ether; if UCP is present, the ether layer will reveal a reddish fluorescence under a Wood's lamp. This test is strongly positive when the whole blood concentration of lead exceeds 80 mg/dl. Treatment is with EDTA (calcium disodium edetate) which chelates lead. In children who die of acute lead encephalopathy, the brain is massively swollen, with herniation of the temporal lobes and cerebellum.
Mercury poisoning arises in two forms, one due to inorganic compounds and the other, more dangerous , to organic mercury (seen in laboratory chemists). This patient presents with the more chronic form due to inorganic compounds, which occurs in persons exposed to large amounts of the metal used in the manufacture of thermometers, mirrors, incandescent lights, X-ray machines, and vacuum pumps. If exposure is more than a minimal degree over a long period, gastrointestinal disturbances are prone to occur (anorexia, weight loss), as well as stomatitis and gingivitis with loosening of the teeth. Diagnosis is with 24 hour urine sample (appears to be more sensitive than serum in chronic poisoning). Normal is less than 20 mcg/L; symptoms develop at or > 200 mcg/L; remove from occupational exposure if > 300 mcg/L. Toxicity in chronic exposure can be see at levels of 50 to 100 mcg/L. Normally employes at hazardous occupations are required to have a baseline urine test when they start work and the test is repeated every 3 to 6 months depending on the risk. Treatment is with DMSA (2, 3 - dimercaptosuccinic acid) administered orally and appears to chelate mercury selectively.
Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency.
Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the blood increase the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide. Arsenic in cells clearly stimulates the production of hydrogen peroxide (H2O2). When the H2O2 reacts with certain metals such as iron or manganese it produces a highly reactive hydroxyl radical. Inorganic Arsenic trioxide found in ground water particularly affects voltage-gated potassium channels, disrupting cellular electrolytic function resulting in neurological disturbances, cardiovascular episodes such as prolonged qt interval, neutropenia, high blood pressure, central nervous system dysfunction, anemia, Leukemia, and death. Arsenic trioxide is a ubiquitous molecule present in American drinking water.
Symptoms of arsenic poisoning begin with headaches, confusion and drowsiness. As the poisoning develops, convulsions and changes in fingernail pigmentation may occur. When the poisoning becomes acute, symptoms may include diarrhea, vomiting, blood in the urine, cramping muscles, hair loss, stomach pain, and more seizures. The organs of the body that are usually affected by arsenic poisoning are the lungs, skin, kidneys, and liver. The final result of arsenic poisoning is coma or death.
Dementia with Lewy-body
Dementia with Lewy bodies overlaps clinically with Alzheimer's disease and Parkinson's disease, but is more associated with the latter. In DLB, loss of cholinergic (acetylcholine-producing) neurons is thought to account for degeneration of cognitive function (similar to Alzheimer's), and loss of dopaminergic (dopamine-producing) neurons for degeneration of motor control (similar to Parkinson's) - in some ways, therefore, it resembles both diseases. The overlap of neuropathologies and presenting symptoms (cognitive, emotional, and motor) can make an accurate differential diagnosis difficult. In fact, it is often confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia), although, where Alzheimer's disease usually begins quite gradually, DLB often has a rapid or acute onset, with especially rapid decline in the first few months. DLB tends to progress more quickly than Alzheimer's disease. Despite the difficulty, a prompt diagnosis of DLB is important because of the risks of sensitivity to neuroleptic drugs and because appropriate treatment of symptoms can improve life for both the person with DLB and their caregivers.
DLB is distinguished from the dementia that sometimes occurs in Parkinson's disease by the time frame in which dementia symptoms appear relative to Parkinson symptoms. Parkinson's disease with dementia (PDD) would be the diagnosis when dementia onset is more than a year after the onset of Parkinson's. DLB is diagnosed when cognitive symptoms begin at the same time or within a year of Parkinson symptoms.
A 55-year-old man, premorbidly described by his family as "thoughtful, accomplished, and intelligent," began neglecting his home and work responsibilities over a 2-year period. He became increasingly inflexible and uncaring. At work he missed several deadlines, and clients complained that he "forgot" about them. Consequently, he stopped working. He became more impulsive, driving late at night without reason. He obsessively checked his furnace numerous times each day and night, unconcerned about this safety risk.
His wife became increasingly tearful and anxious, whereas he seemed unaware of her turmoil and his change in personality. The patient's personal hygiene declined; he stopped shaving and dressed sloppily. At social functions, he interrupted conversations, touched people inappropriately, and spoke in a tasteless and loud fashion, often embarrassing his wife. Despite these changes, he continued to garden and perform other favored activities, albeit with less attention to detail.
Examination results revealed a malodorous and unshaven man with disheveled clothes. He spoke out of turn and was repetitive, stating, 'I have to go." At times he attempted to leave the examination room but returned with gentle coaxing. His affect was otherwise flat. He gave concrete, terse responses to questions, mostly affirmative, negative, or stating, "I don't know." Naming was impaired. He followed some simple commands, but more complex sequences were incomplete or disorganized. His memory was relatively intact, although retrieval of relatives' names was impaired. He listed only 5 animals in 1 minute, a significant impairment given his postgraduate education level. Other than motor impersistence and mild rooting reflex bilaterally, the results of the neurologic examination were relatively unremarkable. Over the next 2 years, the patient became increasing withdrawn, spoke less, and required prompting for virtually every activity.
The most likely diagnosis is
Parkinson's dementia complex
Alzheimer's is the most common cause of dementia among older adults. The major pathogenesis is the production and accumulation of beta-amyloid peptide, bringing about the formation of neurofibrillary tangles, oxidation and lipid peroxidation, glutamatergic excitotoxicity, inflammation, and activation of the cascade of apoptotic cell death. Furthermore, the other hypothesis regarding the pathophysiology of AD stresses tau-protein abnormalities, heavy metals, vascular factors, and viral infections. The natural course of AD averages 10 years. The cardinal features are insidious onset, progressive course, and early memory loss; at least one other cognitive impairment such as language dysfunction, apraxia, agnosia, visuospatial disorder, as well as executive dysfunction, must be seen. These impairments should constitute a decline from the previous level of cognitive functioning, interfering with daily activities.
Memory decline is the hallmark of cognitive change in AD. It is characterized as a storage deficit, meaning that material cannot be recalled with cue. In the early stage, memory impairment for recent events is common whereas long-term memory remains intact. As the disease progresses, individuals with AD are increasingly unable to recall more distant memories. Typically, the motor signs are absent early in the course. Likewise, sensory abnormalities, seizures, and gait difficulties are uncommon until the late phase of disease. Behavioural changes, including depression, anxiety, apathy, aggression, agitation, wandering, vocalization, disinhibition, and abnormal eating, are common thereafter and cause caregiver stress as well as greater need for additional health care services.
There are several clinical syndromes of vascular dementia (VaD), categorized into multi-infarct dementia,
single strategic infarct (single brain infarct damaging functionally critical areas of the brain such as angular gyrus, thalamus, basal forebrain, posterior cerebral artery, and anterior cerebral artery territories),
genetic forms (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), and hypoxic ischemic encephalopathy.
A number of mechanisms causing these clinical syndromes are hemorrhage, ischemia/thrombosis, vasospasm, low perfusion, hematologic and rheological problems.
Since cases do not share common etiology and mechanism, patients may have different clinical presentations. For example, the onset may be abrupt or insidious. The progression may be stepwise, fluctuating, or marked by continuous worsening. Frequently, individuals with VaD present with gradual and progressive cognitive decline without any stroke events. However, typical cases of VaD are usually seen with atherosclerotic co-morbidities (diabetes mellitus, hypertension, coronary heart disease, and peripheral artery disease). The onset of cognitive decline is either subtle or abrupt, and there is psychomotor slowing, executive dysfunction, focal cognitive deficits and motor signs. The temporal association between the cerebrovascular event and the onset of dementia should be within 3 months. Nevertheless, as VaD is variable, sometimes the temporal association cannot be demonstrated easily due to an unclear onset of vascular event.
Dementia with Lewy bodies (DLB)
DLB is claimed to be the second most common type of degenerative dementia among older adults, accounting for 10-15% of cases at autopsy. The criteria for diagnosis of DLB are highly specific but not sensitive. Core clinical features are fluctuating cognitive impairment (50-75%), visual hallucinations, and parkinsonism (seen in 25-50% of patients at diagnosis). Its supportive features are repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusion, hallucination of other modalities, REM sleep behavior disorder, and depression. Physicians frequently encounter patients with dementia and parkinsonism, and a number of differential diagnoses should be raised such as multi-infarct dementia, normal pressure hydrocephalus, and Parkinson-plus syndrome.
Answer: D, Frontotemporal dementia
The clinical features of frontotemporal dementia (FTD) are described with the emphasis on prominent personality and behavioral changes with less prominent memory loss early in the course. Frequently, FTD is misdiagnosed as personality disorders or late-onset psychiatric disorders. Common behaviors and conduct disturbances are loss of personal awareness, loss of social comportment, disinhibition, impulsivity, distractibility, hyperorality (e.g., excessive eating), social withdrawal, stereotyped or preservative behavior, and speech output change (e.g., reduction of speech, stereotype of speech, and echolalia). The physical examination usually reveals early prominent primitive or frontal reflexes. 50% of patients have a family history of dementia in a first-degree relative. There are three principal varieties of FTD: frontal variant FTD (Pick's disease), semantic dementia, and progressive nonfluent aphasia. Physicians usually
misdiagnose FTD if semantic dementia and progressive nonfluent aphasia are present because these two subtypes do not have prominen behavioral or personality disturbance like the frontal variant FTD (Pick's disease).