Portal de Periódicos da CAPES

68-Year-Old Woman With Confusion

2009; Elsevier BV; Volume: 84; Issue: 8 Linguagem: Inglês

10.4065/84.8.737

1942-5546

Mohammed K. Saghir, Kathrin Czarnecki, Murali K. Duggirala,

Epilepsy research and treatment

A 68-year-old woman with a history of chronic obstructive pulmonary disease and bipolar disorder presented to our medical center with a 1-month history of confusion. She was fatigued and confused and had poor oral intake. In the past 2 months, she had lost 10 kg. Two weeks before admission, she started to exhibit atypical behaviors, such as walking about her house undressed. The patient denied fever, headaches, seizures, nuchal rigidity, visual changes, weakness, dysarthria, dysphagia, and bowel or bladder incontinence. She was evaluated at another institution for her symptoms about 2 weeks before. Work-up at that time included electroencephalography, which showed generalized slowing consistent with metabolic encephalopathy. The patient received a 7-day course of ciprofloxacin for delirium that was presumed to be secondary to a urinary tract infection. Her symptoms did not improve with antibiotic therapy, so she presented to our institution for further evaluation. The patient had a long-standing history of bipolar disorder and anxiety treated by a psychiatrist. Her medications included divalproex, lithium, quetiapine, fluphenazine, and clonazepam. Her psychiatric medications had not changed recently, and her mood disorder had been stable for many years. Her other medication was tolterodine, which she had been using for urinary incontinence. The patient and her husband owned a small business, and she had been in charge of the accounting up until 2 months before hospital admission. She smoked 2 packs of cigarettes daily for many years and denied alcohol consumption or drug abuse. Physical examination revealed an elderly woman in no acute distress. She was somnolent but arousable and followed instructions. Her affect was flat, and language was remarkable for simple 1-word answers. Her vital signs and general physical examination findings were normal. Neurologic examination revealed an altered mental status with deficits in attention, learning, and recall. She scored 24 out of 38 points on the Kokmen Short Test of Mental Status, with deficits in attention, learning, and recall. Cranial nerves and motor and sensory functions were normal. Reflexes were symmetric, and plantar response was flexor. The patient's gait was normal, and she had no ataxia. Chest radiography and electrocardiography performed on admission were unremarkable. Noncontrast computed tomography (CT) of the head revealed several small hypodense areas in periventricular white matter consistent with small vessel disease. Laboratory studies (reference ranges provided parenthetically) were remarkable for a hemoglobin of 9 g/dL (12.0-15.5 g/dL) and a mean corpuscular volume of 81 fL (81.6-98.3 fL). Levels of electrolytes, blood glucose, and serum creatinine, transaminases, ammonia, lithium, and valproic acid were within normal or therapeutic range, as were findings on arterial blood gas analysis, urinalysis, and urine drug screening. 1.Which one of the following is the most likely cause of the patient's delirium? a.Bacterial meningitisb.Viral encephalitisc.Metabolic encephalopathyd.Medication-induced deliriume.Subdural hematoma In reviews of the presentation of bacterial meningitis, approximately 99% to 100% of affected patients present with at least 1 of the following: fever, neck stiffness, or change in mental status.1Durand ML Calderwood SB Weber DJ et al.Acute bacterial meningitis in adults: a review of 493 episodes.N Engl J Med. 1993; 328: 21-28Crossref PubMed Scopus (1157) Google Scholar Our patient's 1-month history of delirium without fever or meningeal signs argues against the typical presentation of bacterial meningitis. Numerous viral agents can cause an encephalitis or meningoencephalitis with varying clinical presentation, including herpes simplex virus, enteroviruses, echoviruses, coxsackieviruses, mumps, human immunodeficiency virus, and arboviruses. Affected patients may exhibit a maculopapular exanthem, grouped dermal vesicles, flaccid paralysis, fever, headache, nuchal rigidity, or mental status changes. Our patient's prolonged duration of delirium in the absence of fever and headaches and without focal neurologic findings on examination was not consistent with viral encephalitis. A variety of conditions can cause a metabolic encephalopathy, including hepatic or renal impairment and endocrinopathies. Physical examination findings and laboratory evaluation in our patient were not consistent with a hepatic or uremic encephalopathy. Delirium is caused by medications in up to 30% of all cases.2Francis J Drug-induced delirium: diagnosis and treatment.CNS Drugs. 1996; 5: 103-114Crossref Scopus (51) Google Scholar Our patient was taking multiple psychiatric medications. The combination of lithium with dopamine antagonists such as fluphenazine has been reported to cause weakness, dyskinesias, and encephalopathy.3Chen B Cardasis W Delirium induced by lithium and risperidone combination [letter].Am J Psychiatry. 1996; 153: 1233-1234PubMed Google Scholar The patient's benzodiazepine and anticholinergic agent could also have contributed to her altered mental status. Thus, a careful review of medications is essential in evaluating delirium for all patients. Subdural hematoma was unlikely in this patient given the findings on CT of the head. Careful review of the patient's records showed no recent changes in her psychiatric medications and a mood disorder that had been stable for many years. Additional history indicated exposure to mosquitoes and tick bites several months earlier. The patient had always lived in the Midwest in a farmhouse adjacent to a large forest. Drinking water was obtained from a home well. She had no remarkable travel history. The patient owned a cat but denied recent cat scratches. A lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed an opening pressure of 14 cm H2O, 1 nucleated cell/mL, a glucose level of 51 mg/dL (serum glucose, 91 mg/dL), and a protein level of 54 mg/dL (14-45 mg/dL). Cerebrospinal fluid Gram stain, bacterial cultures, and polymerase chain reaction were negative for cytomegalovirus, herpes simplex virus, Epstein-Barr virus, and varicella zoster virus. Urine and blood cultures showed no growth. Morning cortisol, thyroid-stimulating hormone, free thyroxine, serum folate, and vitamin B12 levels were within normal limits. Over the next several days, the patient's quetiapine, clonazepam, fluphenazine, and tolterodine were tapered and discontinued. Her mental status, however, showed little improvement. Magnetic resonance imaging (MRI) of the brain showed mild to moderate cortical atrophy along with periventricular and subcortical white matter changes consistent with small vessel disease. No evidence of recent infarction was seen. 2.Which one of the following diagnostic tests would be least appropriate in this patient? a.Cerebrospinal fluid arbovirus antibody analysisb.Borrelia burgdorferi serum enzyme-linked immunosorbent assay with CSF antibody analysisc.Bartonella henselae antibody analysisd.Fluorescent treponemal antibody absorption teste.Urine arsenic assay Findings on CSF analysis are not suggestive of viral meningitis. However, cases have been documented to occur with normal CSF findings.4Onorato IM Wormser GP Nicholas P Normal CSF in bacterial meningitis.JAMA. 1980; 244: 1469-1471Crossref PubMed Scopus (77) Google Scholar Arboviral infections of the central nervous system can present as meningitis, meningoencephalitis, or encephalitis and should remain in the differential diagnosis for this patient given her history of exposure. Lyme meningitis is usually associated with a CSF pleocytosis and often occurs in late summer to fall. The onset of neuroborreliosis, however, is variable and occasionally includes the triad of meningitis, cranial neuritis, and radiculitis. Lyme and Bartonella encephalitis should be considered given the history of exposure to tick bite and cat. Neurosyphilis, which can manifest as personality changes in addition to hyperreflexia, paresthesias, and tabes dorsalis, should be evaluated in this patient. Heavy metal toxicity can occur from contaminated well water. However, the neurologic symptoms of long-term arsenic poisoning are primarily limited to polyneuropathy with only very rare cases of encephalitis among individuals with an occupational exposure to arsenic,5Morton WE Caron GA Encephalopathy: an uncommon manifestation of arsenic poisoning?.Am J Ind Med. 1989; 15: 1-5Crossref PubMed Scopus (69) Google Scholar making this the least likely answer. During her hospital stay, the patient's mental status continued to wax and wane. Later, she developed diffuse muscle weakness that was not present on admission. Physical examination confirmed the presence of proximal muscle weakness. Because of the patient's variable mental condition, it could not be determined whether the muscle weakness was secondary to pain. 3.Which one of the following diagnostic approaches would be the most appropriate next step in evaluating the patient's delirium? a.Electromyographyb.Vastus lateralis muscle biopsyc.Computed tomography of the chest, abdomen, and pelvisd.Initiation of antidelirium reorientation techniquese.Measurement of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and creatinine kinase levels Electromyography may be useful for evaluating proximal muscle weakness or the presence of peripheral neuropathy. However, determining the presence of a neuropathy may not elucidate the etiology behind the patient's presenting symptom of confusion. Moreover, the patient's symptoms had been present only a few days, making it too early in the patient's course to see typical changes of most neuromuscular diseases on electromyography. Clinical suspicion of myopathy is an indication for muscle biopsy. Both polymyositis and dermatomyositis could present with proximal muscle weakness in patients of this age. However, preliminary studies such as serum creatinine kinase measurement and electromyography should be performed before initiating this relatively invasive procedure. Moreover, the patient's mental status changes are inconsistent with the presentation of most leading causes of myopathy. Computed tomography of the chest, abdomen, and pelvis could be useful in locating occult malignancy or infection. However, the lack of evidence of a mass on MRI of the head argues against metastatic spread to the brain. Moreover, the patient had no fever, leukocytosis, or localizing history and physical examination findings to suggest hidden infection. Reorientation techniques are important in the treatment of delirium, particularly in patients with prolonged hospitalizations and disrupted sleep/wake cycles. Although such techniques should certainly be considered for this patient, it is unlikely that delirium secondary to unfamiliar environment explains the patient's presentation. Her symptoms began before her hospitalization, and her proximal muscle weakness suggests an underlying etiology that merits investigation. The course of the patient's delirium in combination with progressive systemic symptoms such as muscle weakness should prompt an evaluation for vasculitis. Thus, checking serum markers of inflammation would be most appropriate. Measurement of creatinine kinase is appropriate in the evaluation of proximal muscle weakness. During the hospital stay, the patient became increasingly obtunded. Although she had run a home business in the past, she could no longer perform simple arithmetic calculations nor was she aware of her name or current location. Her upper and lower extremity weakness persisted, and she required moderate assistance in sitting from a supine position. She had symptoms of jaw claudication. Serum anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, and creatine kinase levels were normal. The patient had an elevated serum ESR (106 mm/1 h [0-29 mm/1 h]) and CRP level (147 mg/L [<8.0 mg/L]). Electroencephalography was performed to reevaluate the generalized slowing seen on her outside study. Diffuse slowing of 6 to 7 Hz with intermittent diffuse delta waves was seen with maximal distribution over the bitemporal head regions. 4.Which one of the following is the most appropriate next step? a.Empiric corticosteroids and temporal artery biopsyb.Cerebral angiographyc.Paraneoplastic CSF analysisd.Positron emission tomography/single-photon emission computed tomography of the braine.Psychiatric evaluation for pseudodementia Although a rare manifestation, giant cell arteritis (GCA) can present with mental status changes. Jaw claudication can also be a presenting symptom with GCA. Studies indicate that patients with GCA who have an ESR greater than 100 mm/1h have constitutional symptoms more often than visual symptoms.6Gonzalez-Gay MA Lopez-Diaz MJ Barros S et al.Giant cell arteritis: laboratory tests at the test of diagnosis in a series of 240 patients.Medicine (Baltimore). 2005; 84: 277-290Crossref PubMed Scopus (136) Google Scholar Investigation of GCA along with empiric corticosteroid treatment should take place before other diagnoses are pursued. Although a primary central nervous system vasculitis is a possibility, the combination of a normal CSF study and MRI of the head makes this extremely unlikely.7Calabrese LH Duna GF Lie JT Vasculitis in the central nervous system.Arthritis Rheum. 1997; 40: 1189-1201PubMed Google Scholar As such, cerebral angiography is unlikely to provide useful information. If paraneoplastic causes of altered mental status were in the differential diagnosis, a work-up for neoplasm should be performed before a paraneoplastic analysis of CSF. Little in the patient's history and findings on imaging studies suggested an active neoplasm. Positron emission tomography and single-photon emission computed tomography of the brain show promise for earlier detection of Alzheimer disease. However, the course of the patient's presentation and her elevated inflammatory markers should prompt evaluation of other etiologies before investigating the generally more slowly developing neurodegenerative diseases. Likewise, the elevated ESR suggests an organic cause for her symptoms that should be evaluated before pursuing a diagnosis of pseudodementia. The patient denied any headaches or visual changes. Examination of the temporal region revealed no arterial tenderness, and temporal pulses were normal. A biopsy was performed on the right temporal artery, and the pathology showed vascular inflammation consistent with GCA. 5.Which one of the following is not part of the management plan for this patient? a.Daily prednisone treatmentb.Aspirin, 81 mg/dc.Periodic ESR monitoringd.Annual chest radiographye.Anticoagulation therapy with warfarin Prednisone (40-60 mg/d) is the first-line therapy for GCA. Initiation of corticosteroid therapy is encouraged before obtaining the confirmatory biopsy specimen to prevent visual complications. The incidence of visual loss after the initiation of corticosteroid therapy is approximately 6%.8Aiello PD Trautmann JC McPhee TJ Kunselman AR Hunder GG Visual prognosis in giant cell arteritis.Ophthalmology. 1993; 100: 550-555PubMed Scopus (308) Google Scholar Without corticosteroids, 50% of patients with GCA experience visual changes, and 10% to 50% can have a degree of visual loss. In retrospective studies, the use of daily aspirin in patients with GCA was associated with a lower incidence of cerebrovascular ischemic events.9Lee MS Smith SD Galor A Hoffman GS Antiplatelet and anticoagulant therapy in patients with giant cell arteritis.Arthritis Rheum. 2006; 54: 3306-3309Crossref PubMed Scopus (224) Google Scholar Remission and relapse of GCA after the initiation of treatment is gauged symptomatically and by monitoring ESR. In approximately 15% of GCA cases, the aorta and aortic root are involved, and the condition itself is associated with the development of thoracic aortic aneurysms.10Eberhardt R Dhadly M Giant cell arteritis: diagnosis, management, and cardiovascular implications.Cardiol Rev. 2007; 15: 55-61Crossref PubMed Scopus (42) Google Scholar To that end, yearly monitoring with chest radiography is recommended. Some physicians choose to monitor such cases with serial CT of the chest. The use of warfarin was not associated with a significantly decreased incidence of ischemic cerebrovascular events compared with daily aspirin.9Lee MS Smith SD Galor A Hoffman GS Antiplatelet and anticoagulant therapy in patients with giant cell arteritis.Arthritis Rheum. 2006; 54: 3306-3309Crossref PubMed Scopus (224) Google Scholar The patient began taking 60 mg/d of prednisone and was discharged to a rehabilitation facility. Her delirium and muscle weakness improved during the next month. On follow-up examination 3 months later, the patient was noted to be much more alert, conversant, and cognizant on examination than during her previous admission. She was able to give a concise history. Moreover, she had no visual deficits or weakness. Her ESR and CRP levels had returned to normal range. Giant cell arteritis is a chronic vasculitis of medium and large vessels. It is commonly seen in individuals older than 50 years and of Scandinavian descent. An epidemiological study in Olmsted County revealed an annual incidence of 1 in 4200 people older than 60 years.11Salvarani C Gabriel SE O'Fallon WM Hunder GG The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern.Ann Intern Med. 1995; 123: 192-194Crossref PubMed Scopus (305) Google Scholar The classic presentation of GCA is fever and headache with localization to the temporal region in a patient older than 50 years. Physicians are taught to quickly recognize this typical pattern and intervene to prevent the dreaded complication of vision loss. However, the clinician should also be aware of atypical presentations. In an evaluation of 463 patients with GCA presenting to Mayo Clinic, 2 had confirmed intracranial arterial involvement.12Salvarani C Giannini C Miller DV Hunder G Giant cell arteritis: involvement of intracranial arteries.Arthritis Rheum. 2006; 55: 985-989Crossref PubMed Scopus (116) Google Scholar The symptoms of these 2 patients included progressive deterioration of memory, stupor, confusion, and extremity weakness. Laboratory evaluation for GCA usually reveals a substantially elevated ESR; normochromic, normocytic anemia; and a mild leukocytosis. The criterion standard for diagnosing GCA remains temporal artery biopsy, which typically reveals vasculitic changes with multinucleated giant cells in the arterial wall, predominantly in the media near the internal elastic lamina. However, treatment should not be delayed in the setting of high clinical suspicion. The diagnosis can still be made on the basis of pathologic findings after several days of treatment with corticosteroids. In patients with high clinical suspicion of GCA and negative findings on unilateral temporal artery biopsy, a biopsy of the contralateral side should be performed. Pathologic changes can be focal, with areas of normal vessel anatomy within wider areas of vasculitic changes, necessitating resections at least 2.5 cm in length for adequate evaluation. Corticosteroid therapy remains the standard treatment for GCA. In a widely used regimen, prednisone therapy is initiated at 40 to 60 mg/d, and the dose is gradually tapered on the basis of the clinical condition and the level of inflammatory markers. Treatment generally needs to be continued for 2 years on the basis of improvement in constitutional symptoms, vascular symptoms, and ESR. Adverse effects of long-term corticosteroid treatment, such as hyperglycemia, osteoporosis, and increased risk of infections, need to be taken into consideration. To decrease unwarranted adverse effects, corticosteroid-sparing agents such as methotrexate, cyclophosphamide, and anti—tumor necrosis factor α monoclonal antibody therapy are occasionally used. Daily low-dose aspirin has been suggested to decrease the incidence of cranial ischemic events.9Lee MS Smith SD Galor A Hoffman GS Antiplatelet and anticoagulant therapy in patients with giant cell arteritis.Arthritis Rheum. 2006; 54: 3306-3309Crossref PubMed Scopus (224) Google Scholar Yearly chest radiography is also recommended to monitor for the development of a thoracic aortic aneurysm. Giant cell arteritis is the most common systemic vasculitis affecting elderly patients in Western countries. The classic presentation of GCA with headache and visual symptoms is well recognized, but it is also important to make the diagnosis when patients present with atypical symptoms such as those of our patient. Although atypical symptoms are rare, recognizing and treating patients with atypical presentations can lead to a substantial decrease in morbidity.