TOXIC/METABOLIC DISORDERS 11.1 Central Pontine Myelinolysis A 56-year-old alcoholic was found obtunded in the street. He was found to have a serum sodium of 114 mEq/L, which was aggressively corrected by the emergency department (ED) to a value of 144 mEq/L in the next few hours. Images 11.1A and 11.1B: Axial T2-weighted and fluid-attenuated inversion recovery (FLAIR) images demonstrate hyperintensity in the center of the pons with sparing of corticospinal tracts (red arrow), the “trident” sign. Images 11.1C–11.1E: Axial FLAIR and coronal T2-weighted images demonstrate hyperintensity in the central pons (blue arrows) and striatum (red arrows) in a patient with CPM. 1. Singh TD, Fugate JE, Rabinstein AA. Central pontine and extrapontine myelinolysis: a systematic review. Eur J Neurol. December 2014;21(12):1443–1450. 2. Huq S, Wong M, Chan H, Crimmins D. Osmotic demyelination syndromes: central and extrapontine myelinolysis. J Clin Neurosci. July 2007;14(7):684–688. Epub 2007 April 25. 3. Brown WD. Osmotic demyelination disorders: central pontine and extrapontine myelinolysis. Curr Opin Neurol. December 2000;13(6):691–697. 11.2 Familial Cerebrovascular Ferrocalcinosis A 43-year-old man presented with dystonia and choreoathetoid movements, and was paranoid that his neighbors were spying on him. Images 11.2A–11.2D: Axial CT images demonstrate dense bilateral calcification of the dentate nuclei of the cerebellum, basal ganglia, and pulvinar nucleus of thalamus. Images 11.2E and 11.2F: Axial and coronal T1-weighed images demonstrate basal ganglia hyperintensities (red arrows) in a patient with familial cerebrovascular ferrocalcinosis. 1. Wider C, Dickson DW, Schweitzer KJ, Broderick DF, Wszolek ZK. Familial idiopathic basal ganglia calcification: a challenging clinical-pathological correlation. J Neurol. May 2009;256(5):839–842. 2. Rosenberg DR, Neylan TC, el-Alwar M, Peters J, Van Kammen DP. Neuropsychiatric symptoms associated with idiopathic calcification of the basal ganglia. J Nerv Ment Dis. January 1991;179(1):48–49. 3. Saleem S, Aslam HM, Anwar M, et al. Fahr’s syndrome: literature review of current evidence. Orphanet J Rare Dis. October 2013;8:156. 11.3 Hepatic Encephalopathy A 65-year-old alcoholic man presented with several days of confusion and jaundice. On exam, he did not know the date, location, or his age. He had ascites and asterixis. Images 11.3A–11.3D: Noncontrast axial, coronal, and sagittal T1-weighted images demonstrate hyperintensity (red arrows) of the globus pallidus descending into the cerebral peduncles without mass effect in a patient with hepatic encephalopathy. Table 11.3.1 Causes of Hepatic Encephalopathy Category Causes Excessive nitrogen Gastrointestinal bleeding, renal failure, constipation, high protein diet Electrolyte or metabolic disturbance Hyponatremia, hypokalemia (often from diuretic therapy), hypoxia, hypoglycemia, alkalosis Toxic Benzodiazepines, opiates, antidepressants, antipsychotics, alcohol, valproic acid Infection Pneumonia, urinary tract infection, bacterial peritonitis Focal hepatic pathology Hepatocellular carcinoma, hepatic vein or portal vein thrombosis Table 11.3.2 West Haven Criteria 1. Rovira A, Alonso J, Córdoba J. MR imaging findings in hepatic encephalopathy. AJNR Am J Neuroradiol. October 2008;29(9):1612–1621. 2. Ellul MA, Gholkar SA, Cross TJ. Hepatic encephalopathy due to liver cirrhosis. MJ. August 2015;351:h4187. 3. Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95–110. 4. Córdoba J, Mínguez B. Hepatic encephalopathy. Semin Liver Dis. February 2008;28(1):70–80. 11.4 Cerebellar Atrophy A 34-year-old man with history of seizures since childhood presented with chronic gait ataxia. Images 11.4A and 11.4B: Axial T1-weighted and sagittal T2-weighted images demonstrate atrophy of cerebellum due to chronic antiepileptic therapy. Image 11.4C: Gross pathology demonstrates cerebellar atrophy. 1. Ney GC, Lantos G, Barr WB, Schaul N. Cerebellar atrophy in patients with long-term phenytoin exposure and epilepsy. Arch Neurol. August 1994;51(8):767–771. 2. Shams’ili S, Grefkens J, de Leeuw B, et al. Paraneoplastic cerebellar degeneration associated with antineuronal antibodies: analysis of 50 patients. Brain. June 2003;126(Pt. 6):1409–1418. Unless otherwise stated, all pathology images in this chapter are from the website http://medicine.stonybrookmedicine.edu/pathology/neuropathology and are reproduced with permission of the author, Roberta J Seidman, MD, Associate Professor. Unauthorized reproduction is prohibited. 11.5 Cyclosporin Toxicity A 56-year-old kidney transplant patient developed confusion and headache after being started on a medication. Images 11.5A–11.5D: Axial FLAIR images demonstrate confluent white matter hyperintensities, primarily in the posterior temporal and occipital lobes in a patient treated with cyclosporine. 1. Magnasco A, Rossi A, Catarsi P, et al. Cyclosporin and organ specific toxicity: clinical aspects, pharmacogenetics and perspectives. Curr Clin Pharmacol. September 2008;3(3):166–173. 2. Shah AK. Cyclosporine A neurotoxicity among bone marrow transplant recipients. Clin Neuropharmacol. March–April 1999;22(2):67–73. 3. Edwards LL, Wszolek ZK, Normand MM. Neurophysiologic evaluation of cyclosporine toxicity associated with bone marrow transplantation. Acta Neurol Scand. November 1996;94(5):358–364. 11.6 Heroin Leukoencephalopathy A 45-year-old heroin addict was found sleeping on the street. He was lethargic and disoriented in the ED. Over the next few weeks, he developed diffuse weakness, hyperreflexia, and tremors. Images 11.6A–11.6D: Axial FLAIR images demonstrate symmetric hyperintensities in the subcortical white matter (yellow arrow), posterior limb of the internal capsule (blue arrow), cerebral peduncles (pink arrow), corticospinal tract (red arrow) and medial lemniscus (green arrow) in the pons, and cerebellum in a patient who smoked heroin. 1. Initial symptoms include: 2. After 2 to 4 weeks, 50% of patients develop worsening cerebellar symptoms and additional features: 3. Several weeks after this, 25% of patients enter the terminal stage, which is characterized by: 1. Kass-Hout T, Kass-Hout O, Darkhabani MZ, Mokin M, Mehta B, Radovic V. “Chasing the dragon”—heroin-associated spongiform leukoencephalopathy. J Med Toxicol. September 2011;7(3):240–242. 2. Hagel J, Andrews G, Vertinsky T, Heran MK, Keogh C. “Chasing the dragon”—imaging of heroin inhalation leukoencephalopathy. Can Assoc Radiol J. October 2005;56(4):199–203. 3. Bach AG, Jordan B, Wegener NA, et al. Heroin spongiform leukoencephalopathy (HSLE). Clin Neuroradiol. December 2012;22(4):345–349. 11.7 Marchiafava–Bignami Disease A 61-year-old man with alcoholism presented with rapid-onset dementia. Image 11.7A: Sagittal FLAIR image demonstrates hyperintensity in the central layers of the corpus callosum in a patient with Marchiafava–Bignami disease, the “sandwich” sign. 1. Hillbom M, Saloheimo P, Fujioka S, Wszolek ZK, Juvela S, Leone MA. Diagnosis and management of Marchiafava-Bignami disease: a review of CT/MRI confirmed cases. J Neurol Neurosurg Psychiatry. February 2014;85(2):168–173. 11.8 B12 Deficiency A 36-year-old man presented with severe burning and tingling in his feet, legs, and hands for several months. He had recently attended several music festivals where he abused nitrous oxide. On examination, he was weak in his legs with an unsteady gait. He was unable to feel a tuning fork on his legs and had profoundly impaired joint-position sense. Images 11.8A and 11.8B: Sagittal and axial T2-weighted images of the cervical spine demonstrate hyperintensities in the dorsal columns (red arrows). Images 11.8C and 11.8D: Postcontrast sagittal and axial T1-weighted images of the cervical spine demonstrate hyperintensities in the dorsal columns (red arrows) and the “inverted-V” sign. Image 11.8E: A hypersegmented neutrophil (image credit courtesy of and copyright by Gabriel Caponetti [2014]; from https://commons.wikimedia.org/wiki/File:Hypersegmented_neutrophil_-_by_Gabriel_Caponetti,MD.jpg). 1. Sen A, Chandrasekhar K. Spinal MR imaging in Vitamin B12 deficiency: Case series; differential diagnosis of symmetrical posterior spinal cord lesions. Ann Indian Acad Neurol. April–June 2013;16(2):255–258. 11.9 Copper Deficiency Myelopathy A 56-year-old woman presented with an unsteady gait and pain in her feet several years after undergoing gastric bypass surgery. Images 11.9A and 11.9B: Sagittal and axial T2-weighted images of the cervical spine demonstrate a long segment hyperintensity in the dorsal columns (red arrows). 1. Jaiser SR, Winston GP. Copper deficiency myelopathy. J Neurol. June 2010;257(6):869–881. doi:10.1007/s00415-010-5511-x. Epub March 16, 2010. 2. Kumar N, Gross JB Jr, Ahlskog JE. Copper deficiency myelopathy produces a clinical picture like subacute combined degeneration. Neurology. July 2004;63(1):33–39. 3. Kumar N, Ahlskog JE, Klein CJ, Port JD. Imaging features of copper deficiency myelopathy: a study of 25 cases. Neuroradiology. February 2006;48(2):78–83. Epub October 28, 2005. 11.10 Wernicke’s Encephalopathy A 64-year-old alcoholic man presented with confusion and ataxia. On exam, he was delirious, not knowing the date or location. He was unable to adduct either eye. Images 11.10A and 11.10B: Postcontrast axial T1-weighted images demonstrate enhancement of the mammillary bodies (red circles and arrow). Image 11.10C: Gross pathology demonstrates petechiae in the mammillary bodies. Images 11.10D and 11.10E: Axial FLAIR and diffusion-weighted images demonstrate hyperintensity and restricted diffusion of the posterior thalamus (yellow arrows). Images 11.10F and 11.10G: Axial T2-weighted images demonstrate atrophy of the mammillary bodies (yellow arrows). Image 11.10H: A normal MRI is shown for comparison. 1. Manzo G, De Gennaro A, Cozzolino A, Serino A, Fenza G, Manto A. MR imaging findings in alcoholic and nonalcoholic acute Wernicke’s encephalopathy: a review. Biomed Res Int. 2014;2014:503596. 2. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical settings and recent advances in diagnosis and management. Lancet Neurol. May 2007;6(5):442–455. 3. Zuccoli G, Pipitone N. Neuroimaging findings in acute Wernicke’s encephalopathy: review of the literature. AJR Am J Roentgenol. February 2009;192(2):501–508. Unless otherwise stated, all pathology images in this chapter are from the website http://neuropathology-web.org and are reproduced with permission of the author, Dr. Dimitri Agamanolis. Unauthorized reproduction is prohibited. 11.11 Radiation Necrosis A 39-year-old man presented with seizures and a right homonymous hemianopsia several years after being treated with radiation for an arteriovenous malformation (AVM). Images 11.11A and 11.11B: Axial FLAIR image and catheter angiogram demonstrate an AVM in the left occipital lobe due to an AVM. Images 11.11C and 11.11D: Axial FLAIR images demonstrate hyperintensity of the lesion and reactive edema after radiation. 1. Acute encephalopathy is due to disruption of the blood–brain barrier and occurs in the first month. 2. Early delayed complications occur after 1 to 4 months and are characterized by vasogenic edema and demyelination. Patients may present with encephalopathy or a return of their original tumor symptoms. 3. Radiation necrosis occurs after months to years. Patients present with seizures, recurrence of the initial tumor symptoms, or signs of increased intracranial pressure (ICP) if there is enough edema and mass effect. 1. Miyatake S, Nonoguchi N, Furuse M, et al. Pathophysiology, diagnosis, and treatment of radiation necrosis in the brain. Neurol Med Chir (Tokyo). 2015;55(Suppl. 1):50–59. 2. Na A, Haghigi N, Drummond KJ. Cerebral radiation necrosis. Asia Pac J Clin Oncol. March 2014;10(1):11–21. 3. Parvez K, Parvez A, Zadeh G. The diagnosis and treatment of pseudoprogression, radiation necrosis and brain tumor recurrence. Int J Mol Sci. July 2014;15(7):11832–11846. 11.12 Carbon Monoxide A 45-year-old man was found unconscious, his wife dead beside him. Images 11.12A–11.12C: Axial FLAIR, diffusion-weighted, and apparent diffusion coefficient map images demonstrate symmetric hyperintensity and restricted diffusion (red arrow) in the globus pallidus. 1. Roderique JD, Josef CS, Feldman MJ, Spiess BD. A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement. Toxicology. August 2015;334:45–58. 2. Dubrey SW, Chehab O, Ghonim S. Carbon monoxide poisoning: an ancient and frequent cause of accidental death. Br J Hosp Med (Lond). March 2015;76(3):159–162. 3. Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. March 2009;360(12):1217–1225. 11.13 Transient Signal Alterations in Splenium of Corpus Callosum A 61-year-old man with epilepsy presented with several seizures in one day. Images 11.13A and 11.13B: Axial and sagittal FLAIR images demonstrate hyperintensity within the splenium of the corpus callosum, the boomerang sign. 1. Hirsch KG, Hoesch RE. Boomerang sign on MRI. Neurocrit Care. 2012 Jun;16(3):450–451. 2. Malhotra HS, Garg RK, Vidhate MR, Sharma PK. Boomerang sign: Clinical significance of transient lesion in splenium of corpus callosum. Ann Indian Acad Neurol. April–June 2012;15(2):151–157. 3. Doherty MJ, Jayadev S, Watson NF, Konchada RS, Hallam DK. Clinical implications of splenium magnetic resonance imaging signal changes. Arch Neurol. March 2005;62(3):433–437.
Case History
Diagnosis: Central Pontine Myelinolysis
Introduction
Central pontine myelinolysis (CPM) is a demyelinating disorder that occurs when there is rapid correction of hyponatremia leading to changes in cell osmolarities and shifts of free water. Patients typically have had severe hyponatremia (less than 120 mEq/L) for at least 48 hours.
Clinical Presentation
CPM occurs most commonly in alcoholics or chronically malnourished, medically ill patients. It presents with parkinsonism, quadriparesis, locked-in syndrome, bulbar dysfunction, and coma. Symptoms appear 48 to 72 hours after the correction of hyponatremia.
Radiographic Appearance and Diagnosis
On T2-weighted images, there is hyperintensity in the central pons with sparing of the corticospinal tracts, creating the “trident” sign. Extrapontine myelinolysis occurs in about 10% of patients, most commonly in the caudate and putamen. Other affected locations include the ventrolateral thalami, the external and extreme capsules, and the gray–white matter junction.
Treatment
Treatment of CPM is supportive. It can be fatal in up to 25% of cases, and many survivors are left with permanent neuropsychiatric dysfunction.
To avoid CPM, patients with severe hyponatremia should have their sodium corrected at a rate of no more than 12 to 20 mmol/L daily.
References
Case History
Diagnosis: Familial Cerebrovascular Ferrocalcinosis
Introduction
Familial cerebrovascular ferrocalcinosis (Fahr’s disease) is a rare, autosomal-dominant disease characterized by abnormal calcium deposition in the brain.
Clinical Presentation
It presents with a variety of movement disorders, including parkinsonism, dystonia, chorea, as well as neuropsychiatric impairment. Symptoms typically start in the fourth or the fifth decade, though some patients present younger.
Radiographic Appearance and Diagnosis
It is characterized by bilateral, symmetric calcifications of the basal ganglia, thalamus, dentate nucleus of the cerebellum, and occasionally the subcortical white matter. These are best seen on CT.
There is a variable appearance on MRI, but often calcium crystals will appear hyperintense on unenhanced T1-weighted images.
Calcification of the basal ganglia may be associated with hypoparathyroidism and abnormalities of phosphate and calcium. Serum calcium, phosphorus, magnesium, alkaline phosphatase, calcitonin, and parathyroid hormone should also be measured to rule out metabolic causes. It may also occur after neurocysticercosis or tuberculosis. Often no cause is found.
Treatment
There is no specific treatment for the disease beyond trying to alleviate the symptoms.
References
Case History
Diagnosis: Hepatic Encephalopathy
Introduction
Hepatic encephalopathy occurs in cirrhotic patients when there is diversion of portal venous blood into the systemic circulation.
It can be caused by a variety of pathologies (see Table 11.3.1).
Clinical Presentation
Patients present with neuropsychiatric dysfunction, which may range from mild confusion to coma. Movement disorders, such as asterixis and parkinsonism, are common. It can present acutely, especially if there is a precipitating infection. Such cases may be fatal. The degree of impairment is categorized by the West Haven criteria (see Table 11.3.2).
Radiographic Appearance and Diagnosis
Noncontrast T1-weighted images demonstrate bilateral, symmetric hyperintense lesions in the basal ganglia, most commonly the globus pallidus. These are believed to be due to impaired metabolism of metals, manganese in particular, but are not specific for hepatic encephalopathy. On T2-weighted and diffusion-weighted images, there may be swelling and hyperintensity of the cortex, as well as the thalami, and posterior limbs of the internal capsules. These findings are more common with acute cases and are reversible.
In addition to elevated hepatic function tests, ammonia levels are commonly elevated, though the level does not correlate with functional impairment.
An electroencephalogram (EEG) will classically reveal triphasic waves.
Treatment
Specific treatment depends on addressing the underlying cause. General treatment includes lactulose, which decreases ammonia production and absorption, and antibiotics (such as rifaximin) to decrease ammonia-producing bacteria in the gut. L-ornithine and L-aspartate (LOLA) can be used to remove ammonia by converting it into urea. Supplementation of branched-chain amino acids and the use of probiotics have shown benefit. Restriction of dietary protein is no longer recommended as many patients are chronically malnourished.
Liver transplantation is curative in appropriate patients.
References
Case History
Diagnosis: Cerebellar Atrophy
Introduction
A number of toxins, namely older antiepileptic medications such as phenytoin and alcohol, can result in atrophy of the cerebellum with chronic use.
Patients with neurodegenerative diseases, such as olivopontocerebellar atrophy and the spinocerebellar ataxias, have a similar clinical and radiographic presentation.
Paraneoplastic cerebellar degeneration (PCD) can occur with a number of malignancies due to production of antineuronal antibodies that target Purkinje cells throughout the cerebellar cortex. Gynecologic cancers are most commonly implicated, though the condition is rare overall, occurring in less than 1% of cancers. Ovarian and breast cancers are associated with anti-Yo and anti-Ri antibodies, lung cancer is associated with anti-Hu antibodies, and Hodgkin’s lymphoma is associated with (anti-Tr and anti-mGluR1) antibodies.
Clinical Presentation
Patients develop a wide-based, ataxic gait, slurred, scanning speech, and nystagmus. The arms are relatively spared with toxic cerebellar degeneration.
With PCD, symptoms can develop rapidly over the course of several months. Patients then stabilize, but are often debilitated by their symptoms.
Radiographic Appearance and Diagnosis
The superior vermis is affected earliest and the cerebellar hemispheres are affected only in the most severe cases. Skull thickening can also be seen with long-term use of phenytoin.
Treatment
There is no treatment beyond stopping the offending medication or alcohol use. PCD responds poorly to immunotherapy. With nongynecologic cancers, the condition may improve with treatment of the underlying neoplasm.
References
Case History
Diagnosis: Cyclosporine
Introduction
Cyclosporine is an immunosuppressant medication used to prevent organ rejection in transplantation. Neurotoxicity occurs in up to 25% of patients, especially when high doses are used. Breakdown of the blood brain barrier is the likely mechanism.
Clinical Presentation
Patients present with seizures, cortical blindness, headaches, psychosis, and encephalopathy. Electrolyte abnormalities are a risk factor.
Radiographic Appearance
White matter hyperintensities are seen on T2-weighted images primarily in the parietal and occipital lobes. They may be seen more diffusely throughout the brain in severe cases. Microhemorrhages may be seen as well.
Treatment
In the vast majority of patients, symptoms resolve with lowering the dose or drug cessation.
References
Case History
Diagnosis: Heroin Leukoencephalopathy
Introduction
“Chasing the dragon” is a method of smoking heroin that involves placing a powder on an aluminum foil, which is then heated underneath. The vapor is then inhaled. It is known to produce a spongiform leukoencephalopathy.
Clinical Presentation
The syndrome progresses over several stages.
Soft speech
Ataxia
Restlessness
Cognitive changes, most commonly apathy
Spastic weakness and hyperreflexia
Tremor and myoclonus
Chorea and athetosis
Hypotonic paresis and areflexia
Akinetic mutism
Central pyrexia
Spasms
Death in certain cases
Radiographic Appearance and Diagnosis
On MRI the pattern is typical for a toxic leukoencephalopathy. It is characterized by symmetric, hyperintensity on T2-weighted images of the subcortical white matter, posterior limb of the internal capsule, the corticospinal tract, and the cerebellum. The gray matter and subcortical u-fibers are typically uninvolved.
Treatment
Treatment is supportive.
References
Case History
Diagnosis: Marchiafava–Bignami Disease
Introduction
Marchiafava–Bignami disease is a rare disorder characterized by symmetrical areas of demyelination and necrosis, primarily of the corpus callosum (CC).
Clinical Presentation
It occurs most commonly in middle-aged, male alcoholics, but may occur in any chronically malnourished patient. It presents with a rapid-onset dementia and is thought to be due to a deficiency of vitamin B complex.
Radiographic Appearance and Diagnosis
Imaging abnormalities characteristically start in the body of the CC and later involves the genu and then splenium. It preferentially involves the central layers with sparing of peripheral dorsal and ventral layers, a finding known as the “sandwich sign” on sagittal MRI imaging.
Treatment
Replacement of B vitamins may result in improvement in some patients.
Reference
Case History
Diagnosis: Subacute Combined Degeneration
Introduction
B12 (cyanocobalamin) is involved in fatty acid and amino acid metabolism, as well as DNA synthesis and regulation. It cannot be produced endogenously, and is obtained entirely through dietary sources.
Deficiencies may occur in strict vegetarians, patients with inflammatory bowel disease, postgastric bypass patients, patients with impaired absorption of B12 (pernicious anemia), or in patients who abuse nitrous oxide. Certain medications, namely proton pump inhibitors and histamine 2 receptor antagonists, can also decrease B12 absorption. Overall, pernicious anemia is the most common cause. Gastric parietal cells are destroyed in an autoimmune process, leading to atrophic gastritis and a deficiency of intrinsic factor, a protein necessary for B12 absorption in the ileum. It usually presents in older adults.
Clinical Presentation
Deficiency causes accumulation of methylmalonic acid and neurological dysfunction in the peripheral nerves, optic nerves, dorsal and lateral columns of the spinal cord, and the brain. It is the combined degeneration of the dorsal and lateral columns that led to the term subacute combined degeneration.
Patients can experience a wide range of symptoms, including neuropathy, myelopathy, or neuropsychiatric manifestations. Typically, patients develop a cold sensation, numbness, or tingling that starts in the toes and then ascends up the legs, eventually involving the fingertips and hands. Some patients may experience excruciating lancinating pains. Limb weakness and gait ataxia can be seen in advanced cases. Patients may develop neuropsychiatric manifestations including depression and psychosis. Cognitive dysfunction is common and may be severe enough to cause frank dementia.
Neurological examination initially reveals impaired vibration and joint-position sense, which progresses over time to loss of light touch, pain, and temperature. The feet and legs are affected before arms. The ankle jerks are absent, with relative hyperreflexia at the knees. The bait is wide-based and Romberg sign is usually positive.
Systemic signs and symptoms include shortness of breath, tachycardia, weight loss, nausea, and pallor. Patients may have a smooth, beefy red tongue and impaired taste, and sores at the corner of the mouth (angular cheilitis).
Hematological findings include hypersegmented neutrophils and a macrocytic anemia. When combined with the neuropsychiatric dysfunction, B12 deficiency is called “megaloblastic madness.”
Radiographic Appearance and Diagnosis
As seen in Images 11.8A and 11.8B, in patients with myelopathy, spine MRI may reveal hyperintensities in the dorsal columns on T2-weighted images. In exceptional cases, there may be enhancement of the dorsal columns. This produces the “inverted-V” sign.
Spinal cord atrophy can be seen in chronic cases. A similar clinical and radiographic pattern can occur in patients with HIV-associated myelopathy.
Serum studies may reveal a macrocytic anemia, and hypersegmented neutrophils are seen on peripheral smear.
Importantly, patients can experience neurological symptoms with low–normal B12 values. Elevated levels of homocysteine and methylmalonic acid are the most sensitive markers of B12 deficiency.
Patients with an unclear etiology for their deficiency should be evaluated for pernicious anemia by testing for antiparietal cell and intrinsic factor antibodies.
Treatment
Treatment is with replacement of B12. Though injections are often needed initially, high doses of oral B12 are sufficient in most patients, even those with pernicious anemia. Neurological symptoms will stabilize, but not improve with treatment, however.
Reference
Case History
Diagnosis: Copper Deficiency Myelopathy
Introduction
Copper deficiency myelopathy (CDM) is an acquired, noncompressive myelopathy, which closely mimics subacute combined degeneration due to vitamin B12 deficiency.
Etiologies for impaired copper absorption in the upper gastrointestinal tract include prior gastric surgery, zinc overload, and various malabsorption syndromes. In some cases, no cause is found.
CDM is most common in patients in their 40s and 50s, and women are more commonly affected than men.
Clinical Presentation
Patients present with a slowly progressive gait ataxia and paresthesias in the hands and feet. Polyneuropathy is a near universal finding.
Neurological examination will reveal:
Wide-based ataxic and spastic gait and spastic paraparesis
Sensory ataxia and impaired vibration and joint-position sense
Sensory loss in a stocking–glove distribution and/or a sensory level
Positive Romberg sign
Radiographic Appearance and Diagnosis
MRI is the imaging modality of choice, though it may be normal in half of the patients. Spinal MRI demonstrates long segment hyperintensities on T2-weighted images in the posterior columns of the cervical and/or thoracic spinal cord.
The diagnosis can be confirmed by detecting low serum copper and ceruloplasmin levels. Copper levels are usually decreased in the urine, in contrast to Wilson’s disease. Elevated zinc levels are common. Anemia and neutropenia are common findings as well.
Treatment
CDM is treated with copper supplementation, which can stabilize symptoms, though many patients do not improve. The radiographic abnormalities may improve with treatment as well.
References
Case History
Diagnosis: Wernicke’s Encephalopathy
Introduction
Wernicke–Korsakoff encephalopathy is due to a deficiency of thiamine (vitamin B1). It most commonly occurs in patients with chronic alcoholism, but can also occur in patients with poor nutritional intake due to eating disorders or prolonged vomiting, patients on chronic parenteral nutrition, or as a complication of bariatric surgery or gastric malignancies.
Clinical Presentation
Wernicke’s encephalopathy is characterized by the triad of delirium, ataxia, and ophthalmologic abnormalities, including nystagmus, ophthalmoparesis, and impaired pupillary reaction. Few patients present with this complete triad, and the most common symptoms are confusion and memory impairment. Most individuals have a 4- to 6-week store of thiamine; however, acute deficiency states can be triggered by glucose loading in patients with already low thiamine levels.
Korsakoff’s psychosis is a more advanced form of the illness characterized by anterograde and retrograde amnesia, confabulation, and psychosis. It often follows Wernicke’s encephalopathy in alcoholics, but is less common in other etiologies.
Radiographic Appearance and Diagnosis
T2-weighted image MRI reveals symmetrical hyperintensity in the mammillary bodies, medial thalami, quadrigeminal plate, and periaqueductal area.
As seen in Images 11.10A and 11.10B, enhancement on postcontrast imaging is frequently seen, especially in alcoholics. Atrophy of the mammillary bodies is seen in chronic cases.
Treatment
Treatment is with thiamine replacement.
References
Case History
Diagnosis: Radiation Necrosis
Introduction
Therapeutic radiation is used to treat cerebral malignancies and AVMs.
Radiation necrosis refers to postradiation brain necrosis. Blood vessels are acutely vulnerable to radiation, leading to vasogenic edema. Oligodendrocytes are also vulnerable to radiation, leading to demyelination.
Clinical Presentation
There are three stages of radiation-induced central nervous system (CNS) injury:
Radiographic Appearance
There are a variety of radiographic appearances. On T2-weighted images, there is typically edema in the white matter with mass effect. With the addition of contrast, there may be cystic enhancement.
It may be difficult to distinguish radiation-induced changes from tumor recurrence. MR perfusion studies may be helpful in this setting, as tumors show increased relative cerebral blood volume, while radiation necrosis does not.
Over time, there is atrophy of the necrotic area.
Treatment
Treatment is indicated in patients with symptoms due to mass effect and increased ICP. Steroids can be used, and are most effective in the acute and early delayed stages.
References
Case History
Diagnosis: Carbon Monoxide Poisoning
Image 11.12D: Gross pathology demonstrates multiple punctate hemorrhages in the globus pallidus.
Introduction
Carbon monoxide (CO) is a colorless, odorless, tasteless, gas. CO combines with hemoglobin to form carboxyhemoglobin, which in turn prevents oxygen from binding to hemoglobin.
Clinical Presentation
With mild cases, patients develop nonspecific symptoms such as nausea, headache, and fatigue. In more severe cases, patients develop apathy, rigidity, bradykinesia, and dystonia. In severe cases it is fatal. Patients may experience a delayed deterioration several weeks after the initial insult, manifested by depression, memory loss, and psychosis.
Radiographic Appearance and Diagnosis
On T2-weighted images, there is hyperintensity and restricted diffusion in the globus pallidus. Other characteristic findings are hippocampal and cerebellar injury and diffuse cerebral edema. Carboxyhemoglobin in the serum confirms the diagnosis.
Treatment
Acute treatment involves administering 100% oxygen or hyperbaric oxygen therapy, which hastens the removal of CO from hemoglobin.
References
Case History
Diagnosis: Transient Hyperintensity of the Splenium of Corpus Callosum
Introduction
The corpus callosum (CC) is the largest white matter tract connecting the two cerebral hemispheres. It is divided into three parts. From anterior to posterior these are the genu, body, and splenium.
Transient signal alterations in splenium of the CC are most commonly seen in patients suffering from focal status epilepticus or in patients who abruptly stop antiepileptic medications. A wide variety of other pathologies can cause this finding including infections, hypoglycemia, trauma, hyponatremia/hypernatremia, infections, posterior reversible encephalopathy syndrome, thiamine deficiency in alcoholics, hemolytic–uremic syndrome with encephalopathy, and hemicrania continua.
Clinical Presentation
Confusion and delirium are the most common presentations. Patients do not typically suffer from disconnection syndromes, such as alexia without agraphia, seen in other lesions of the splenium of the CC.
Radiographic Appearance and Diagnosis
There is hyperintensity on T2-weighted images involving the splenium of the CC. The radiographic appearance is known as the “boomerang” sign. The lesions are transient and improve or entirely resolve on subsequent imaging.
Treatment
Treatment is directed at the underlying cause. There is generally a good prognosis.
References
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