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Home arrow Psychology arrow Neuropsychiatric Symptoms of Cognitive Impairment and Dementia

Infectious Disorders

Most central nervous system (CNS) infections present with an acute change in mental status, but some develop more insidiously, mimicking a neurodegenerative dementia.

Human immunodeficiency virus (HIV) disease can cause cognitive impairment as a result of primary HIV disease, opportunist infectious and malignancies, toxic effect of medication, and depression, due to psychosocial consequences associated with HIV infection. HIV-associated neurocognitive disorders (HAND) are characterized by a triad of cognitive impairment, behavioral changes, and motor dysfunction [59]. Cognitive impairment can result in mental slowness, problem-solving and decision-making difficulties, perseveration, and impairment of attention, memory, and/or learning [60]. Apathy and social withdrawal are neuropsychiatric manifestations that may occur and resemble depression. A progressive and disabling impairment in motor function can also ensue, including hyperreflexia, hypertonia, ataxia, tremor, bradykinesia, and postural instability [59]. Diagnosis is based in the clinical features, brain MRI and CSF, to exclude other opportunist complications. Several categories of HAND can be established, depending on interference in everyday functioning: asymptomatic neurocognitive impairment, mild neurocognitive impairment, and HIV-associated dementia (HAD). In patients treated with combination antiretroviral therapy (cART), intellectual impairment is attenuated and the temporal course prolonged, and, therefore, HAD has been less common despite a high frequency of milder stages of HAND [61]. Early recognition and management of HIV infection with cART to suppress the HIV viral load may effectively limit, or even improve, neurocognitive impairment [62 ] . Additional supportive therapies should be used to control other neuropsychiatric symptoms. In the context of HIV infection and cognitive impairment, opportunistic CNS neoplasms and infections should be actively investigated because they have specific treatments that could successfully halt or improve the intellectual decline, such as CNS lymphoma, progressive multifocal leukoencephalopathy due to JC virus reactivation, cryptococcal meningitis, toxoplasmosis, and cytomegalovirus and varicella-zoster virus encephalitis.

Neurosyphilis refers to the infection of the CNS by a sexually acquired disease caused by a spirochete organism, Treponema pallidum subspecies pallidum. It was common in the pre-antibiotic era occurring at any time after initial infection in up to 40 % of patients with syphilis [50]. Neuropsychiatric symptoms caused by syphilis usually occur in the late stage, representing a form of tertiary syphilis, the so- called general paresis (also known as general paralysis of the insane or paralytic dementia), and it accounted for a few cases of neurosyphilis. Early symptoms include memory loss, irritability, insomnia and personality change. A progressive dementing illness may evolve over many years, resulting in confusion and disorientation, loss of judgment, and also seizures and psychiatric symptoms, such as depression, mania, and psychosis. Physical examination may be normal, but commonly reveals dysarthria, hypomimia and limb hypotonia, facial and limb intention tremor, hyperreflexia and, in the setting of ]abes dorsalis] sensory ataxia, and Argyll Robertson pupil [63]. The diagnosis is based on clinical examination and serum and CSF data. Serum evaluation in late syphilis shows a nontreponemal test (such as rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL)) either positive or falsely negative, but specific treponemal tests (such as Treponema pallidum hemagglutination assay (TPHA) or fluorescent treponemal antibody absorption (FTA-ABS)) remain persistently positive regardless of previous treatment. CSF with pleocytosis and increased protein concentration is consistent with neurosyphilis. VDRL in CSF is very specific for neurosyphilis, but has a low sensitivity, meaning that a reactive CSF-VDRL establishes the diagnosis of neurosyphilis, but a nonreactive test does not rule out the diagnosis, providing a role to more sensitive but less specific tests, like CSF FTA-ABS. Parenteral penicillin remains the mainstay of effective treatment.

Lyme neuroborreliosis (LNB) is an infection disorder of the nervous system caused by the tick-borne spirochete Borrelia burgdorferi. The neurological features are diverse and typically include lymphocytic meningitis and peripheral nervous system manifestations (radiculopathy, plexopathy, polyneuropathy, multiple mononeuropathy, cranial neuropathy, particularly facial palsy) and, rarely, CNS involvement. More than 95 % can be categorized as early LNB, defined as signs and symptoms lasting for less than 6 months. A few cases may have a long-lasting course, between 6 months and several years, facing the late LNB [64]. Neuropsychiatric manifestations may occur in different settings: encephalitis in early LNB, presenting with headache and mental confusion; subacute encephalopathy in late LNB, affecting memory, mood (mainly depressive symptoms and irritability), excessive daytime sleepiness, and, sometimes, subtle symptoms of language disturbance with difficulty in finding words; chronic progressive Lyme encephalitis or encephalomyelitis, also in late LNB, most frequently presenting with a tetraspas- tic syndrome, spastic-ataxic gait disorder, bladder dysfunction and subtle memory impairment, and lesions of the periventricular white matter; and, finally, in postLyme disease syndrome, characterized by nonspecific subjective symptoms, including fatigue, difficulties in sleeping, and cognitive impairment, that persist for more than 6 months after standard treatment for Lyme disease [64-66]. The diagnosis of LNB is based on several issues: known exposure through Ixodes tick bite; a clinical history recalling an early localized disease that occurred a few days to 1 month after the tick bite, consisting in local skin infection (erythema migrans) and other associated manifestations (malaise, mild headache and neck stiffness, myalgias, arthralgias, regional lymphadenopathy); objective clinical evidence of nervous system involvement and of other systems (musculoskeletal, skin, heart, eye, liver); and laboratory evaluation. Lyme antibody tests in serum can be detected in nearly 100 % of the patients with Lyme disease after 6 weeks of symptom duration, but their diagnostic specificity are low, because seropositivity occurs in a significant percentage of normal population, and antibodies may persist for years after successful treatment. The diagnostic criteria of active LNB include inflammatory changes of CSF and an elevated specific Borrelia CSF-to-serum antibody index, indicating intrathecal Borrelia antibody production, which is usually detected 2-3 weeks after onset of neurological symptoms [64]. LNB should be treated with antibiotics, usually with intravenous ceftriaxone for 2-3 weeks or, in case of allergy, doxycycline is the alternative.

Whipple disease (WD) is a rare, relapsing, slowing progressive, systemic illness caused by a bacterial infection due to a gram-positive bacillus, Tropheryma whipplei . Clinical features are protean, characteristically diarrhea, weight loss, abdominal pain, low fever, night sweats, and polyarthralgias, and fewer than 15-30 % of patients with WD will have neurological manifestations. Neuropsychiatric symptoms are the most frequent manifestations of WD in CNS, comprising cognitive impairment, with or without dementia criteria, and concomitant psychiatric illness, such as depression, hypomania, anxiety, psychosis, and change in personality. Besides neurocognitive changes, neurological involvement in WD, may also include movement disorders (myoclonus, pathognomonic oculo- masticatory myorhythmia, and/or oculofacial-skeletal myorhythmia), eye findings (nystagmus and supranuclear ophthalmoplegia), reduced consciousness, cerebellar ataxia, seizures, and hypothalamic damage (e.g., dysautonomia, emotional impairment, disruptive insomnia, polydipsia, hyperphagia, decreased libido, amenorrhea). Although dementia, ophthalmoplegia, and myoclonus are a highly specific diagnostic triad, it is noted in only nearly 10 % of patients with CNS-WD. Involvement of the CNS was traditionally seen as a late manifestation of WD, generally preceded by other systemic problems; however, it has been now frequently recognized as the initial clinical manifestation of WD, even without the concomitant typical gastrointestinal or joint complaints, leading to a late or misdiagnosis. The diagnostic procedure of CNS-WD is based on tissue biopsy from the symptomatic sites, conventionally duodenal mucosa, and from CSF sample, by showing periodic acid-Schiff (PAS)-positive foamy macrophages and positive polymerase chain reaction (PCR) assay against Tropheryma whipplei. The brain MRI is usually normal or has nonspecific changes, and CSF may show inflammatory signs. Treatment consists in long-term antibiotic therapy which crosses blood-brain barrier (parenteral penicillin and streptomycin for at least 2 weeks followed by cotrimoxazole for 1-2 years) [67].

Subacute and chronic meningitis can present with headache, fever, meningism, change in mental status, cerebral infarctions, hydrocephalus, cranial nerve palsies, seizures, and, occasionally, rapidly progressive cognitive impairment. The most common causative entities are cryptococcal and tuberculous meningitis, but other less frequent fungal infections have been also identified (such as coccidioidomycosis, histoplasmosis, and candidiasis). They are usually seen as an opportunist infection in immunocompromised population, but may occur also in immunocompetent patients in whom the diagnosis may be delayed or missed due to low level of clinical suspicion [68, 69].

Other CNS infections have been, rarely, described as mimics of rapid progressive dementia, including viral encephalitis sometimes presenting a more insidious course; JC and BK virus in immunocompromised population; bacterial agents, such as Mycoplasma pneumoniae, Bartonella henselae particularly in immunosuppression conditions, and Brucella spp. causing chronic neurobrucellosis; and parasitic infections such as cerebral toxoplasmosis as an opportunist infection among immunocompromised patients, neurocysticercosis in endemic countries, and trypanosomiasis and malaria in tropical regions [70].

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