Clinical Implications of Splenium Magnetic Resonance Imaging Signal Changes

ORIGINAL CONTRIBUTION Clinical Implications of Splenium Magnetic Resonance Imaging Signal Changes

Michael J. Doherty, MD; Sumie Jayadev, MD; Nathaniel F. Watson, MD; Ravi S. Konchada, MD; Dan K. Hallam, MD

Background: Magnetic resonance imaging (MRI) may Results: Confusion (35 patients), ataxia (25 patients), show discrete splenium abnormalities; however, the im- and recent seizure (23 patients) were common. Causes plications of this radiologic finding are unclear. included alcohol use, infections, hypoglycemia, trauma, salt abnormalities, and seizure. Twenty-eight patients had Objective: To describe causes, clinical presentations, and complete resolution, 23 improved, and 1 died. Diffusion- prognoses of midline splenium changes evident on MRI. weighted imaging showed splenium abnormalities the best. Eleven of 12 patients showed decrease in apparent Design: Retrospective case series. diffusion coefficient. Most improved clinically, as did their subsequent MRI studies. Setting: Teaching hospital. Conclusions: Midline splenium changes are com- Patients: Medical records of 9 patients with MRI- monly seen on MRI diffusion-weighted imaging se- noted splenium changes were studied; 60 additional pub- quences. Multiple causes can result in splenium changes. lished cases were accessed. Physicians should evaluate for glucose and electrolyte abnormalities, seizure risk, ongoing infectious or parain- Interventions: Sixty-nine cases were reviewed. fectious process, and traumatic causes.

Main Outcome Measures: Clinical and imaging findings, causes, and prognosis. Arch Neurol. 2005;62:433-437

AGNETIC RESONANCE Studies in which radiologic changes were mark- imaging (MRI) stud- edly asymmetric and extended beyond the sple- ies suggest splenium nium, as seen with vascular infarction or ma- injury is common, re- lignancy, were not studied. Symmetric, bilateral versible, and associ- involvement was not excluded. Clinical findings and outcomes were collected. No statis- atedM with multiple origins and presenta- tical hypothesis testing occurred. tions (Table 1); however, the implications of this radiologic finding are unclear. In this series of MRI-evident splenium inju- RESULTS ries, causes are recorded with clinical findings and outcomes. We evaluate records Medical records of 9 patients along with of patients with midline splenium changes 60 published cases with MRI splenium incidentally noted on brain MRI to deter- changes were studied. Of 69 patients evalu- mine if they share a characteristic presen- ated, 52 had clinical outcomes recorded: tation or common cause. The results 28 had complete resolution, 23 im- are discussed and evaluation strategies proved, and 1 died. Causes are given in proposed. Table 1. The vignettes and imaging of Author Affiliations: unique patients evaluated by the authors Departments of Neurology appear in the Figure. Clinical findings of (Drs Doherty, Jayadev, and METHODS Table 2 Watson) and Radiology 58 patients are given in . The most (Drs Konchada and Hallam), This retrospective case series study was per- consistent splenium changes evident from The University of Washington, formed in a teaching hospital. Using MEDLINE MRI were reduced T1 signal intensities, in- and the Swedish Epilepsy keywords splenium and MRI, we accessed and creased T2 and fluid-attenuated inver- Center (Dr Doherty), Seattle. reviewed published cases of splenium changes. sion recovery signals, and, if performed,

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Reporting bias limits the usefulness of the study. Descrip- Table 1. Causes Associated With Splenium Damage tions of patient symptoms, particularly of hemispheric dis- connectionorpsychiatricfindings,weresparse.Inaliterature- Possible Causes Reference(s) based case series, reported causes or clinical findings may Alcohol, alcohol and malnutrition 1-14, PS not parallel what is most common. Follow-up MRI was rare, Trauma 15-16, PS and few reports documented ADC values. Human herpesvirus 6 17 Malaria 18 Rotavirus 19 POSSIBLE INJURY MECHANISMS Measles 20 Salmonella 21 The DWI signal changes suggest restricted movement of Escherichia coli O157 22, 23 free water. The ADC values help clarify this restriction: Human immunodeficiency virus 24 reduced ADC values, as seen in 11 patients, suggest cy- Acute disseminating encephalomyelitis 25, PS totoxic edema; ADC value increases (1 patient) suggest Seizure 6, 17, 23, 26-33, PS vasogenic edema.28,43,44 Patients with increased and de- Altitude sickness 27, 32 Neoplasia 34 creased splenium ADC values may normalize with ad- Radiation therapy 35 ditional imaging, perhaps implying an absence of cyto- Chemotherapy toxic edema. Both ADC reduction and subsequent reversal Fluorouracil 36 are uncommon; associated diagnoses include hemiple- Cyclosporine 37 gic migraine, venous sinus occlusion, and seizure.26,44 Sple- Hypoglycemia 22, PS nium injuries should be added to this list. Hyponatremia 23 Hypernatremia PS In healthy patients who underwent MRI T2 relax- Leukodystrophy 25, 38 ation studies, the splenium and posterior limb of the in- Renal failure 23 ternal capsule displayed heterogeneity in water content; Cerebrovascular accident 39 however, comparison tissue myelin water content was Hypertension or preeclampsia 40, 41 higher.45 The splenium may have easily perturbed cellular fluid mechanics when compared with surround- Abbreviation: PS, present study. ing tissues. Origins associated with splenium injury, including renal failure, hyponatremia, hypernatremia, hypoglycemia, infection, altitude sickness, and thia- increased diffusion-weighted imaging (DWI) (Figure). mine deficiency and alcoholism, can compromise cellu- Splenium abnormalities were easiest to see with DWI in lar fluid regulation. How generalized convulsions might 8 of 9 original cases. Seven of our 9 patients had DWI contribute to splenium DWI and ADC changes is harder changes in posterior limbs of the internal capsules. No to explain. splenium abnormalities were evident in computed to- Convulsions might transiently impair available glu- mograms of the 9 patients reviewed from our institu- cose, leading to brief, reversible failures of cellular fluid tion. Of those same patients, 3 had elevations of cre- regulation. A similar mechanism could explain why atine kinase levels, necessitating directed treatment and hypoglycemic patients develop reversible splenium surveillance. changes. Alternatively, antiepileptic drug toxicity or The DWI was reported with apparent diffusion coef- level fluctuations combined with changes in salt homeo- ficient (ADC) values in 12 patients; all but 1 was re- stasis and resultant myelin edema are other suggested duced.3,15,19,21,26-28 Of those with reductions, 8 of 11 had mechanisms.26-29 complete clinical recovery. In 16 of 18 patients, sple- Not all MRI findings reversed. Persisting changes in- nium abnormalities resolved on follow-up MRI. The DWI cluded cystic lesions within the splenium, although patho- changes and ADC values related to convulsions showed logic correlation was limited.5,6 Magnetic resonance spec- no residual MRI or clinical abnormalities. The patient with troscopy suggests that lactate levels can be abnormal and increased ADC values had complete resolution of MRI may resolve over time; in patient 5, however, no spec- and clinical findings.28 troscopic changes were seen.7

COMMENT CONFUSION, MUTISM, AND HALLUCINATIONS: WHAT IS THE ROLE OF THE SPLENIUM? The MRI-documented splenium changes may be associated with confusion, ataxia, seizure, hemispheric dis- Thirty-five of the patients had confusion and delirium, connection findings, and dysarthria. The most common and hallucinations occurred in at least 4 patients. Pa- clinical finding was altered mental status. The triad of tient 2 is unique, because the presentation included cata- tremor, dementia, and death as described in patients with tonia, increased muscle tone, waxy posturing, and an Marchiafava-Bignami disease was not seen.42 Diagnoses amobarbital response, features similar to catatonic associated with splenium abnormalities varied mark- schizophrenia. Splenium pathologic findings from pa- edly (Table 1). More important, DWI often showed other tients with schizophrenia may show increased fiber thick- areas of involvement, particularly the posterior limbs of ness and preservation of axonal fiber density.46-48 Neu- the internal capsules. The DWI demonstrated splenium roimaging of new-onset schizophrenia demonstrates changes markedly better than other MRI sequences or differing splenium size and diffusion tensor imaging an- computed tomograms. isotropy.49 Both agenesis of the corpus callosum and

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©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Patient No./ Diminished hearing, dizziness, Patient No./ This patient with alcoholism and type Sex/Age, y nausea, and anorexia preceded Sex/Age, y 1 diabetes mellitus was found with 3 days of dysarthric speech. He a blood glucose level of 57 mg/dL 1/M/18 4/M/40 complained of visual and auditory (3.17 mmol/L). He was anorexic, hallucinations. MRI revealed multiple with headache, but refused other T2, FLAIR, and DWI changes, most questions. His creatine kinase level notably in bilateral subcortical and was 10 800 U/L; his urine contained periventricular white matter and ketones. Results from LP were the splenium. The presumptive unremarkable, including oligoclonal diagnosis was acute disseminated banding. Splenium ADC values were encephalomyelitis. Subsequent MRI decreased. showed splenium change resolution.

DWI DWI

2/M/24 A delirious binge-drinker was given 5/M/32 A high-speed vehicle crash resulted benzodiazepines and thiamine. He in femur and humerous fractures. was mute, with waxy posturing and Unexplained focal anisocoria increased tone. He blinked to threat prompted MRI. An ADC map reduc- and clap but failed to withdraw to tion was evident, whereas magnetic pain. His creatine kinase level was resonance spectroscopy results 9112 U/L (reference range, 30-285 were unremarkable. Somnolence U/L). His catatonia prompted an and disorientation improved during amobarbital interview; after injection 3 weeks. waxy posturing remitted. His outstretched arms “helped prevent the hospital from falling [on him].” With amobarbital metabolism, behaviors returned.

DWI DWI

3/F/52 This patient with bipolar disorder had brittle serum sodium levels of 160 to 6/M/44 This patient with type 1 diabetes 170 mEq/L. Hypernatremia was due to prior lithium-induced nephrotoxicity. With mellitus was found down and given sodium correction, psychiatric disturbances would dissipate. On this admission, empiric D50; blood glucose level, the patient’s sodium level was 190 mEq/L; after appropriate correction (including checked after infusion, was 56 mg/dL thiamine), dyskinesias, pressured speech, flight of ideas, hypersexuality, and (3.11 mmol/L). Initially unresponsive, confabulation continued. Her arrest of psychiatric recovery independent of sodium he progressed to baseline by day 5. correction was new. MRI showed T2 and DWI changes in the thalami, subinsular His creatine phosphokinase level was regions, posterior limbs of the internal capsules, hippocampi, the splenium, central 2858 U/L; his blood urea nitrogen midbrain, and cerebral hemispheres, suggesting extrapontine myelinolysis. and creatinine levels were 34 and 2.4 mg/dL (12.14 mmol/L and 212 µmol/L), respectively. Head computed tomogram was unremarkable; MRI showed FLAIR and T2 changes in the splenium, corticospinal tracts, and posterior limbs of the internal capsule.

FLAIR

DWI DWI

Figure. Clinical and imaging review of 6 patients. MRI indicates magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery; DWI, diffusion-weighted imaging; LP, lumbar puncture; ADC, apparent diffusion coefficient; and D50, dextrose (25 g) in 50 mL of buffered water.

schizophrenia in patients suggest that disrupted inter- easily localize. More important, splenium injuries in 7 hemispheric communication predisposes to behavioral of 9 patients occurred, with subtle changes evident in the change and psychosis.50 posterior limbs of the internal capsule. Damage to these Mutism, hallucinations, psychosis, and hemispheric corticospinal pathways could result in marked dysar- disconnection are potentially more specific findings of thria, ataxia, and increased tone. What surprised us was splenium compromise. Still unclear is if and how the sple- that findings of hemispheric disconnection were not com- nium regulates mutism or hallucinations. Perhaps the right mon, potentially illustrating reporting bias. Prospec- and left hemispheres generate independent nonsense, the tive, descriptive studies that used DWI inclusion crite- censure of which is necessary and normal and requires ria might clarify this concession. an intact splenium. PROPOSED EVALUATION IS THERE A SPLENIUM SYNDROME? Splenium changes evident on MRI are not incidental. Al- From this series, nonspecific common findings, such as though infrequently associated with death, the finding ataxia, dysarthria, increased tone, and delirium, do not can suggest treatable causes. A detailed history with re-

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