Case Files Neurology - part 6 pot

Treatment Treatment is with antitoxin. The botulinum immunoglobulin in infants has been shown to shorten the hospital stay and cost of hospitalization. Additionally it has been shown to reduce the severity of illness. Human botulinum immunoglobulin is directed toward type A and B. Supportive care is vital. Patient should be carefully monitored in an ICU setting for impending respi- ratory distress. Additionally, tube feedings and care for the prolonged immo- bility and stress ulcers are needed. The case fatality rate is less than 2%; on average, infants will spend 44 days in the hospital. Rare cases of relapse have been reported with no known predictors identified. Most relapses occur within 2 weeks of being discharged from the hospital. Comprehension Questions [27.1] A 2-month-old baby boy presents with a history of poor suck, irritabil- ity, decreased oral intake, ptosis, head drop, and weakness in the arms and legs. The baby is in foster care, and there is not a good way to obtain a history. While evaluating the baby he develops respiratory dis- tress. Key findings on his examination include external ophthalmople- gia, reactive pupils, ptosis, facial weakness, and weakness in the arms and legs. His DTRs and tone appear to be normal. What is the likely diagnosis? A. Infantile botulism B. Neonatal myasthenia gravis C. Guillain-Barré syndrome D. Meningitis [27.2] In cases of suspected infantile botulism which of the following is the most helpful in evaluating the patient? A. Serum test for botulinum toxin B. CSF studies for botulinum toxin C. EMG with repetitive nerve stimulation studies D. Pharyngeal culture for botulinum toxin [27.3] A 73-year-old man presents to the emergency room complaining of diplopia, blurred vision, dysphagia, and xerostomia. His examination reveals ptosis, impaired ocular motility, dilated pupils, symmetrical weakness in the arms and legs, and normal cognitive function. Which of the following would be most consistent with his presentation? A. Antecedent gastrointestinal disease with nausea, vomiting, and diarrhea B. Loss of sensation in a glove and stocking distribution C. A history of eating honey from California D. Normal EMG with repetitive nerve stimulation studies CLINICAL CASES 233 234 CASE FILES: NEUROLOGY Answers [27.1] B. The presence of reactive pupils and normal deep tendon reflexes points away from infantile botulism. Likewise the presence of normal deep tendon reflexes is unlikely in GBS. The absence of fever makes it unlikely that this is meningitis. [27.2] C. Fecal cultures and not pharyngeal cultures are the best way to diag- nose infantile botulism. EMG with repetitive nerve stimulation studies are key in making the diagnosis of infantile botulism. [27.3] A. This case is illustrative of foodborne botulism, which is known to have normal sensation and normal cognitive function. EMG with repetitive nerve stimulation studies will be abnormal. Botulism from spores in honey occur primarily in infants. CLINICAL PEARLS ❖ Infantile botulism is the most common cause of botulism in the United States. ❖ Infantile botulism is commonly acquired from spores in soil or in honey. ❖ Classic presentation for infantile botulism includes antecedent con- stipation with the ascending paralysis, ptosis, dilated or unreac- tive pupils, and weakness in the arms and legs. ❖ The best way to test for infantile botulism is through stool samples via a mouse bioassay. ❖ More than 70% of these infants with botulism will eventually require mechanical ventilation. REFERENCES Arnon SS, Schecter R, Maslanka SE, et al. Human botulism immune globulin for the treatment of infant botulism. N Engl J Med 2006 Feb 2;354(5):462–471. Cherington M. Clinical spectrum of botulism. Muscle Nerve 1998;21:701–710. Schreiner M, Field E, Ruddy R. Infant botulism: a review of 12 years experience at the Children’s Hospital of Philadelphia. Pediatrics 1991;87:159–165. ❖ CASE 28 A 52-year-old man is referred for further evaluation of mild forgetfulness, poor concentration, and withdrawal from friends. His wife who has accompa- nied him feels that he is clumsier noting that he is often times tripping. The patient has also noticed that he is clumsier and that he is more forgetful and is having difficulty focusing at work. He also notes a reduction in libido. His physical examination is notable for a normal Mini Mental Status Examination (MMSE) but with slowness in answering questions. Cranial nerves and motor strength are normal. Mild fine hand movements are awkward, and there is mild ataxia noted. Deep tendon reflexes are slightly increased. He is concerned because he has been losing weight and is currently awaiting the results of a second HIV test. A previous HIV test 4 weeks ago was positive. ◆ What is the most likely diagnosis? ◆ What is the next diagnostic step? ANSWERS TO CASE 28: HIV-Associated Dementia Summary: A 52-year-old man with weight loss has been experiencing mild for- getfulness, poor concentration, clumsiness, difficulty focusing at work, reduced libido, and withdrawal from friends. His examination shows normal cognitive function by MMSE but mental slowness in answering questions. Mild ataxia and poor coordination of his hands are noted. Additionally he has mild hyperreflexia. His HIV test 4 weeks ago is positive. ◆ Most likely diagnosis: Dementia/HIV-associated dementia (HAD) ◆ Next diagnostic step: Neuropsychologic testing, obtain results of his last HIV tests, MRI of the brain, lumbar puncture for cerebrospinal fluid (CSF) studies Analysis Objectives 1. Be familiar with the diagnosis of HIV associated dementia (HAD). 2. Know how to diagnose and treat HAD. 3. Describe the differential diagnosis of HAD. Considerations This 52-year-old man with a positive HIV test presents with poor concentration, mild forgetfulness, difficulty focusing, withdrawal from friends, clumsiness, and reduced libido. The classic findings of behavioral changes, difficulty with coordination, and mild impaired intellect in the setting of a positive HIV test is likely to be HIV associated dementia (HAD). Depression could also present this way; however, one would not expect there to be problems with coordina- tion. Encephalitis, neurosyphilis, frontal temporal dementia, and HIV-1 associ- ated opportunistic infections are also in the differential diagnosis. These can be distinguished from HAD by performing an MRI of the brain, lumbar puncture, and neuropsychologic testing. Neurologic complications from HIV can be seen from opportunistic infections, drug-related complications, tumors secondary to HIV, and HIV itself. The pathophysiology of HAD is likely multifactorial. First, there is invasion of HIV into the central nervous system. HIV-infected monocytes are thought to enter the brain and infect microglia, astrocytes, neu- rons, and oligodendrocytes. Additionally, the HIV virus may replicate in the cells. Viral toxins or HIV proteins may be directly toxic to neurons or may cause damage by activating macrophages, microglia, and astrocytes, which in turn release chemokines, cytokines, or neurotoxic substances. A cytokine called oncostatin M may be the most damaging of the cytokines, although it acts in concert with other cytokines. Finally, there is evidence to support oxidative stress and increases in excitatory amino acids and intracellular calcium. 236 CASE FILES: NEUROLOGY APPROACH TO HIV-ASSOCIATED DEMENTIA Definitions Ataxia: Unsteady motion of the limbs or trunk or a failure of muscular coordination. Dementia: A disorder characterized by a general loss of intellectual abilities involving memory, judgment, abstract thinking, and changes in personality. Neuropsychological testing: A battery of tests used to evaluate cognitive impairment. It is an extension of the MMSE. HAART: Highly active antiretroviral therapy. Clinical Approach HAD has an incidence of 10.5 cases per 1000 person-years in the United States. This incidence has decreased since HAART was introduced as before HAART (before 1992) the incidence was 21 cases per 1000 person-years. Older patients with HIV have a higher likelihood of having HAD. A poor prognosis has been associated with low CD4 counts, high HIV RNA levels, low body mass index, lower educational levels, and anemia. Most patients with HAD have developed an AIDS-defining systemic illness. A few patients, however, present with only immunosuppression by laboratory criteria. The earliest symptoms of HIV-associated dementia include difficulty with concentration, attention, and slowness of thinking. The forgetfulness is pres- ent early on, and patients have increasing difficulty performing complex tasks. Personality changes begin to appear such as apathy, social withdrawal, and quietness. Dysphoria and psychosis are rare. Psychomotor dysfunction mani- fested by poor balance and lack of coordination follows cognitive dysfunction, although rarely it can be the initial symptom of HAD. Tripping or falling along with poor handwriting are the more common motor symptoms. As the disease progresses, the ataxia worsens and can become disabling. Myoclonic jerks, postural tremor, and bowel and bladder dysfunction can be present in the later stages of the disease. Patients at end stage of the disease are unable to ambulate, have incontinence, and are almost in a vegetative state. Importantly focal neurologic deficits tend to be absent. Early in the disease course, neuropsychologic testing can be normal; however, as time progresses there is evidence of a subcortical dementia. Typical abnormalities include difficulty in concentration, motor manipulation, and motor speed. Mild problems with word finding and impaired retrieval can be present. Eventually, severe psychomotor slowing and language impairment occur. Initially, the neurologic examination is normal, and at this time, subtle impairment in rapid limb and eye movements can be found. As the disease progresses, hyperreflexia, spasticity, and frontal release signs can be found. Additionally apraxia (inability to perform previously learned tasks) and aki- netic mutism (severely decreased motor-verbal output) can develop. CLINICAL CASES 237 Neuroimaging (MRI brain) studies are essential in evaluating patients with AIDS and cognitive impairment. Diffuse cerebral atrophy is typical in HAD. Some patients have white matter changes and abnormalities in the thalamus and basal ganglia (Fig. 28–1). Other conditions which can mimic or cause demen- tia can be excluded by MRI. CSF studies are nonspecific and are performed pri- marily to exclude other diagnoses. These nonspecific findings include a mildly elevated CSF protein (60% of cases) and mild mononuclear pleocytosis (25%). Quantitative HIV polymerase chain reaction (PCR) that evaluates CSF in viral load is the best parameter that relates to HAD. Improvement in CSF viral load leads to improvement in the clinical status of HAD. Differential Diagnosis 1. Cerebral lymphoma 2. Progressive multifocal leukoencephalopathy 3. CNS infections such as cryptococcal meningitis, toxoplasmosis, cytomegalovirus encephalitis, neurosyphilis, histoplasmosis, and coccidioides 4. Toxic metabolic states such as vitamin B 12 deficiency, thyroid disease, alcoholism, medication effect, illicit drug abuse 5. Metastatic malignancy 238 CASE FILES: NEUROLOGY Figure 28–1. T2-weighted MRI in AIDS dementia complex. (With permission from Aminoff MJ, Simon RR, Greenberg D. Clinical neurology, 6th ed. New York: McGraw-Hill/Lange Medical Books; 2005: Fig. 1–16.) Histopathologic findings include atrophy in the frontotemporal distribution with diffuse myelin pallor. Some cortical neuronal loss is noted in 25% of cases. Activated glial cells are twice as frequent as in brains of controls. The management of HAD depends on viral suppression by means of HAART. HAART not only protects against but also induces the remission of HAD. Selective retroviral drugs that enter the CSF can be helpful and include zidovudine, indinavir, and lamivudine. Comprehension Questions [28.1] A 29-year-old male with a history of illicit drug abuse in the past pres- ents with complaints of mild forgetfulness, social withdrawal, and dif- ficulty concentrating. He has a good appetite and has not experienced alteration in his sleep cycle. His neurologic examination including his MMSE is completely normal. His girlfriend has commented that she has seen him stumble more frequently. What is the next step in evalu- ating this individual? A. Obtain neuropsychologic testing to evaluate for personality disorder B. Obtain an MRI of the brain C. Obtain a stat lumbar puncture for CSF studies to exclude meningitis/encephalitis D. Clinically observe and follow the patient [28.2] Which of the following have been associated with a poor prognosis in HAD? A. A history of multiple AIDS defining illnesses with high CD4 counts B. Low CD4 counts, high HIV RNA, and low body mass index C. Head trauma with loss of consciousness prior to becoming HIV positive D. Low CD4 counts, anemia, and low HIV RNA [28.3] A 32-year-old HIV positive man is noted to have forgetfulness, gait disturbance, and confusion. A lumbar puncture is performed, and the India ink preparation is positive. Which of the following is the most likely diagnosis? A. HIV-associated dementia B. Cryptococcal meningitis C. Toxoplasmosis D. CNS lymphoma CLINICAL CASES 239 Answers [28.1] B. The first test to request in evaluating this patient is in imaging study. This will determine whether or not there is increased intracranial pres- sure so that a lumbar puncture can be safely performed. Although neu- ropsychologic testing is required, it is not meant to evaluate solely for a personality disorder. [28.2] B. A history of multiple AIDS defining illnesses would be seen with low CD4 counts and thus would be a poor prognostic factor for HAD. The answer in the question, however, states a high CD4 count. [28.3] B. India ink positive stain is highly suggestive of cryptococcal meningitis. 240 CASE FILES: NEUROLOGY CLINICAL PEARLS ❖ HIV-associated dementia is typically associated with forgetfulness, difficulty concentrating, slowness in thinking, and loss of coordination. ❖ HIV-associated dementia is more commonly seen in individuals with low CD4 counts, high HIV RNA, low body mass index, ane- mia, and low levels of education. ❖ The best way to prevent and reduce the severity of HAD is by using HAART. ❖ AIDS dementia complex (ADC) is divided into two clinical cate- gories: (1) severe form-HIV-associated dementia complex, and (2) less severe form- HIV-associated minor cognitive/motor disorders. ❖ Patients with mild HIV dementia commonly present with depres- sion and anxiety. Therefore, HIV-infected individuals with depression should be screened for early HIV dementia. REFERENCES Dorland’s Illustrated Medical Dictionary, 27th ed. Philadelphia, PA: WB Saunders; 1988. Gibbie T, Mijch A, Ellen S, et al. Depression and neurocognitive performance in individuals with HIV/AIDS: 2-year follow-up. HIV Med 2006 Mar;7(2): 112–121. Kaul M, Lipton SA. Mechanisms of neuronal injury and death in HIV-1 associated dementia. Curr HIV Res 2006 Jul;4(3):307–318. McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol 2004 Dec; 157(1–2):3–10. ❖ CASE 29 A 53-year-old female presents with loss of balance, mood swings, and mem- ory loss. She had not noticed these symptoms until her coworkers and family pointed it out to her. Although these symptoms presented 4 months ago, she did not seek medical attention until now when they began interfering with her daily activities. Her ataxia has progressed to the point that she is stumbling and falling. She has noticed difficulty with problem solving, and her boss has wit- nessed inappropriate behavior. Her family reports that over the past month her memory has quickly deteriorated to the point that she is unable to recognize friends, is unable to drive, is not able to work, and forgets if she has eaten. She has also developed slurred speech and has been witnessed to “jerk” during the day. Your neurologic examination reveals an Mini Mental Status Examination (MMSE) score of 17/30 having difficulty with orientation, object recall, cal- culations, naming, concentration, and drawing the intersecting polygons. There is horizontal nystagmus with moderate dysarthria and anomia noted. Her strength appears to be normal; however, she has dysmetria and a wide- based gait. Her deep tendon reflexes (DTRs) are hyperreflexic, and she has evidence of myoclonus. A CT scan of the brain is performed and shows no abnormalities. ◆ What is the most likely diagnosis? ◆ What is the next diagnostic step? ◆ What is the next step in therapy? ANSWERS TO CASE 29: Sporadic Creutzfeldt-Jakob Disease Summary: A 53-year-old woman presents with a 4-month history of rapidly progressive memory loss, ataxia, mood swings, inappropriate behavior, and dysarthria. Her examination is notable for a markedly abnormal MMSE with global abnormalities, moderate dysarthria, and anomia. She additionally has nystagmus, dysmetria, ataxia, myoclonus, and hyperreflexia. ◆ Most likely diagnosis: Sporadic Creutzfeldt-Jakob disease. ◆ Next diagnostic step: Serologic studies including chemistry 20, complete blood count (CBC), HIV, erythrocyte sedimentation rate (ESR), thyroid- stimulating hormone (TSH), thyroxine (T 4 ), triiodothyronine (T 3 ), vitamin B 12 , rapid plasma reagin (RPR), international normalized ratio (INR), MRI of the brain, lumbar puncture for protein, glucose, cell count with differential, Gram stain and cultures and 14–3-3 protein. Additionally an electroencephalograph (EEG) may be requested. ◆ Next step in therapy: Supportive therapy. Analysis Objectives 1. Be familiar with the clinical presentation of sporadic Creutzfeldt-Jakob disease and its variants. 2. Know the differential diagnosis for Creutzfeldt-Jakob disease. 3. Know how to diagnose Creutzfeldt-Jakob disease. Considerations This 53-year-old woman presents with a rapidly progressive set of neurologic symptoms including memory loss, ataxia, behavioral changes, poor coordina- tion, and myoclonus. These abnormalities are consistent with a rapidly pro- gressive dementia atypical for Creutzfeldt-Jakob disease (CJD). At first, patients experience problems with muscular coordination; personality changes, includ- ing impaired memory, judgment, and thinking; and impaired vision. The CT scan rules out stroke or brain tumor; most other causes of dementia are of slower onset. Nevertheless, in this patient, potentially treatable causes of dementia are sought with the laboratory and MRI tests. 242 CASE FILES: NEUROLOGY [...]... CJD of 66 % and a specificity of 74% (Fig 29–1) Computerized tomography of the brain can help rule out the possibility that the symptoms result from other problems Fp2-F4 F4-C4 C4-P4 P4-O2 Fp2-F8 F8-T4 T4-T6 T6-O2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp1-F7 F7-T3 T3-T5 T5-O1 200 µV 1s Figure 29–1 EEG of a patient with Creutzfeldt-Jakob disease (With permission from Aminoff MJ, Simon RR, Greenberg D Clinical neurology, ... microglial nodules, and astroglial nodules Cases that show marked increased intracranial pressure and herniation are best handled with the aid of neurosurgeons Figure 31–1 CT brain image with ring-enhancing Toxoplasmosis (With permission from Knoop KJ, Stack LP, Storrow AB: Atlas of Emergency Medicine; 2nd ed New York:McGraw-Hill; 20 06: Fig 20–7, p 65 6.) 264 CASE FILES: NEUROLOGY Treatment The main treatment... surrounding edema Additionally there is a 12-mm lesion in the left basal ganglia With the administration of IV contrast, these lesions enhance ◆ What is the most likely diagnosis? ◆ What is the best way to confirm the diagnosis? ◆ What is the next step in therapy? 260 CASE FILES: NEUROLOGY ANSWERS TO CASE 31: Intracranial Lesion (Toxoplasmosis) Summary: A 25-year-old previously healthy man presents to... a glove-and-stocking distribution A Romberg sign is present Cerebellar examination is normal; however, his deep tendon reflexes are diminished (1+/2) in the legs His gait is widebased with marked ataxia ◆ What is the most likely diagnosis? ◆ What is the next step to confirm diagnosis? ◆ What is the treatment plan? 252 CASE FILES: NEUROLOGY ANSWERS TO CASE 30: Tabes Dorsalis Summary: A 58-year-old man... this young woman has suffered significant trauma because her right pupil is not reactive ◆ What is the most likely diagnosis? ◆ What is the next diagnostic step? 268 CASE FILES: NEUROLOGY ANSWERS TO CASE 32: Unreactive Pupil Summary: A 17-year-old female presents to the emergency room with a right frontal headache after being hit by a joystick from a video game She did not lose consciousness and does... of Neurological Disorders and Stroke Creutzfeldt-Jakob disease fact sheet Available at: http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm Zerr I, Pocchiari M, Collins S, et al Analysis of EEG and CSF 14– 3-3 proteins as aids to the diagnosis of Creutzfeldt–Jakob disease Neurology 2000;55:811–815 This page intentionally left blank ❖ CASE 30 A 58-year-old man is referred for evaluation of severe lancinating... frequently seen in early cases of AIDS Treatment consists of penicillin Multiple ring-enhancing lesions as opposed to solitary lesions are suggestive of CNS toxoplasmosis 265 CLINICAL CASES Answers [31.1] C Spores are not part of the life cycle of T gondii [31.2] D Argyll Robertson pupil has not been reported with CNS toxoplasmosis Bladder incontinence, although uncommon, is part of an underlying myelopathy... toxoplasmosis Describe how to treat toxoplasmosis and what precautions are necessary Considerations This 25-year-old healthy man has been experiencing headaches for the past 6 months and just experienced his third generalized tonic-clonic seizure His examination suggests a left-sided brain lesion as he has right-sided motor findings (decreased right arm swing and increased tone on the right) The fact that he... Venereal Diseases) Sex Transm Infect 1999 Aug;75(suppl 1):S34–37 Stevenson J, Heath M Syphilis and HIV infection: an update Dermatol Clin 20 06 Oct;24(4):497–507 ❖ CASE 31 A 25-year-old man is brought to the emergency room after experiencing a generalized tonic-clonic seizure He was getting ready for work when he apparently fell to the floor and had the seizure His mother who witnessed the event states... consists of all of the following except: A B C D E Toxoplasmosis Lyme disease Sarcoidosis Multiple sclerosis Subacute combined degeneration [30.4] A 30-year-old man who abuses IV drugs presents to your office complaining of left-sided weakness for the past 6 weeks His examination is notable for Argyll Robertson pupils, hyporeflexia in the legs and left hemiparesis He is healthy otherwise except for having . NEUROLOGY Fp2-F4 F4-C4 C4-P4 P4-O2 Fp2-F8 F8-T4 T4-T6 T6-O2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp1-F7 F7-T3 T3-T5 T5-O1 200 µV 1 s Figure 29–1. EEG of a patient with Creutzfeldt-Jakob disease. (With permis- sion from. of 66 % and a specificity of 74% (Fig. 29–1). Computerized tomography of the brain can help rule out the possibility that the symptoms result from other problems 2 46 CASE FILES: NEUROLOGY Fp2-F4 F4-C4 C4-P4 P4-O2 Fp2-F8 F8-T4 T4-T6 T6-O2 Fp1-F3 F3-C3 C3-P3 P3-O1 Fp1-F7 F7-T3 T3-T5 T5-O1 200. malignancy 238 CASE FILES: NEUROLOGY Figure 28–1. T2-weighted MRI in AIDS dementia complex. (With permission from Aminoff MJ, Simon RR, Greenberg D. Clinical neurology, 6th ed. New York: McGraw-Hill/Lange