An Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient with Non-traditional Risk Factors

Abstract

Case ReportMr. A is a 52 year old man from Qatar with a past medical history of hypertension, diabetes mellitus type 2, hyperlipidemia, diverticulitis status post hemicolectomy, and cervical stenosis of C5-7 who began experiencing intermittent headaches, episodes of slurred speech, and decreased appetite from April to October 2014. In November 2014, he developed progressive weakness of his right lower extremity over three days, to the extent that he was unable to control his right lower extremity or walk properly. The weakness was associated with intermittent leg pain as well as numbness in both feet. He had no associated bowel or bladder symptoms. He presented to the emergency department of a local institution where an MRI of the brain demonstrated focal atrophy of the left post central and adjacent superior frontal gyri at the vertex with mild white matter T2 hyperintensity. His symptoms persisted and he was transferred to a higher level of care for further evaluation. During that admission he developed he developed new onset right upper extremity weakness in addition to his right lower extremity weakness. The following day, he experienced a focal motor seizure of the right upper and lower extremities. Phenytoin was prescribed and after he had a second seizure and levetiracetam was later added. Repeat MRI of the brain with and without contrast showed a non-enhancing T2 hyperintense lesion involving the left posterior frontal and parietal preand post-central gyri without significant mass effect. Unfortunately, the patient experienced multiple recurrent focal seizures that were resistant to multiple anti-epileptics and was intubated due to declining level of consciousness. A third MRI of the brain showed increased size of the left frontoparietal lesion and expansion into the occipital cortical and subcortical regions, with mild increase in mass effect, and intralesional dark foci on susceptibility weighted imaging concerning for petechial hemorrhage. Viral and bacterial cultures from the patient's cerebrospinal fluid (CSF) showed no growth. The patient was then transferred to our institution for further diagnostic evaluation.Shortly after arrival, the patient underwent repeat lumbar puncture. CSF analysis was notable for positive JC virus polymerase chain reaction. To make a more definitive diagnosis, brain biopsy AbstractProgressive multifocal leukoencephalopathy (PML) is a frequently fatal demyelinating condition of the central nervous system in which reactivation of the human polyomavirus JC (JCV) leads to lytic infection of oligodendrocytes. JCV reactivation typically occurs in the setting of profound impairment of cellular immunity seen in conditions such as human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS), hematologic malignancies, autoimmune diseases, and treatment with immunosuppressive medications. However, an emerging body of literature suggests that minimal or occult immunosuppression may be sufficient for the development of PML in certain cases. We report the ...

Progressive multifocal leukoencephalopathy without overt immunosuppression

“…While PML without overt immunosuppression has been described in the literature, it is considered an exceedingly rare entity. [3–44] However, our single-center retrospective review suggests that PML without overt immunosuppression may make up a substantial proportion of PML cases (11.8%). Of note, prior population-based studies also reported no obvious immunocompromising disease or treatment in 6.3% [38] and 6.5% [45] of PML patients.…”

“…A comprehensive literature review of PML in the absence of overt immunosuppression (Table 1) [3–44,46] showed that previously described cases (median age 61 [range 21–81] years; 26% female) were usually found to have underlying comorbidities that may be associated with some degree of immunosuppression, including idiopathic CD4 lymphocytopenia (17/79; 21.5%), chronic renal failure (7/79; 8.9%) [5,22,26] and liver disease (15/70; 19%) most commonly due to hepatitis (6/79; 7.6%) [5,10] or alcoholism (6/79; 7.6%). [5,7,38,43] While case 2 had significant alcohol consumption in the year prior to diagnosis, both laboratory (liver function tests, coagulation studies) and radiographic (computed tomography abdomen) testing did not yield evidence for liver dysfunction.…”

“…In fact, only 51/74 (68.9%) of reported cases had a fatal outcome, with the remaining patients surviving the disease with significant disability (Table 1). [3–44,46]…”

“…Mirtazapine and mefloquine (some improvement), stable at 34 mo 46 2013 Kastrup et al [21] 57 F HLD, tobacco use Yes BK virus co-infection. Died 6 mo after disease onset 47 2013 Kobayashi et al [22] 81 Izaki et al [24] 77 F None No Responded to mefloquine and improved clinically 53 2015 Liebowitz et al [9] 52 M DM, cirrhosis No Remained alive for mo but dependent for total care 54 2016 van der Kolk et al [25] 49 Miskin et al [29] 66 M ICL (87/uL) No Diagnosed with PML 4 mo after disease onset. IL-7 therapy (increase in ALC and mild improvement), stable at 13 mo 59 2016 Nanda et al [10] 66 M Hep C cirrhosis NR Lost to follow up 60 2016 Grewal et al [7] 55 al [41] A literature review was performed via a comprehensive Pubmed and Google scholar search for papers with the following title or key words: "PML in immunocompetent patients," "PML with occult immunosuppression," "PML with no immunosuppression" and "PML with idiopathic CD4 lymphocytopenia (ICL)."…”

“…[1,2] In immunocompetent patients, PML is considered a rare occurrence but has been described in multiple previous case reports and series. [3][4][5][6][7][8][9][10][11][12][13][14] Prevalence, overall frequency, and prognosis of PML without overt immunosuppression are still largely unknown.…”