Adult Hemophagocytic Lymphohistiocytosis (HLH) with Neurological Involvement: Diagnostic Complexities – A Case Report and Literature Review

Michał J. Sekuła; Anna Jamroz-Wiśniewska; Urszula Chyrchel-Paszkiewicz; Aleksandra Pietruczuk; Aleksandra Dembowska; Maciej Dubaj; Karol Bigosiński; Konrad Rejdak

doi:10.12659/AJCR.947694

19 July 2025 : Case report Poland

Adult Hemophagocytic Lymphohistiocytosis (HLH) with Neurological Involvement: Diagnostic Complexities – A Case Report and Literature Review

Unusual clinical course, Challenging differential diagnosis, Rare disease, Educational Purpose (only if useful for a systematic review or synthesis)

Michał J. Sekuła

^{ADEG 1*}, Anna Jamroz-Wiśniewska

^{ADEG 1}, Urszula Chyrchel-Paszkiewicz

^{BC 1}, Aleksandra Pietruczuk

^{BCF 1}, Aleksandra Dembowska

^{CF 1}, Maciej Dubaj

^{CDF 1}, Karol Bigosiński

^{CD 1}, Konrad Rejdak

^{AEG 1}

DOI: 10.12659/AJCR.947694

Am J Case Rep 2025; 26:e947694

Authors information Article notes Copyright and License information

Introduction Case Report Discussion Conclusions References

Related articles Order reprints Share article Share by email

View HTML version

Table 1 Papers describing HLH with CNS involvement [1,2,7–35].

Authors	Age	Sex	Symptoms	Imaging findings	Etiopathogenesis	Treatment	Results of treatment
He et al []¹	57 years	Male	Disturbance of consciousness, anomalous behavior	Hyperintensity involving the pons, cortical, and subcortical regions	Diffuse large B-cell lymphoma	Dexamethasone, R-CHOP chemotherapy	Remission
Fohle et al []²	51 years	Male	Lightheadedness, confusion	Multiple abnormally enhancing lesions mainly in the right frontal lobe with a small hemorrhagic focus	Unknown	Dexamethasone, etoposide, prophylactic antibiotics, acyclovir	Complete remission
Kim et al []⁷	58 years	Female	Aphasia and cognitive decline for 2 weeks	Hyperintensity in the bilateral subcortical white matter and right periventricular area	SARS-CoV-2 vaccination	Methylprednisolone, immunoglobulins	Death
Ikumi et al []⁸	56 years	Male	Muscle weakness in both legs, multiple sclerosis relapse-like symptoms	–	HSV-2 infection	Methylprednisolone	Death
Nagamura et al []⁹	34 years	Female	Myalgia, proximal muscle weakness, dermatomyositis	–	HSV-1 infection	Azathioprine, acyclovir, steroids, cyclosporine, valacyclovir	Remission
Żur-Wyrozumska et al []¹⁰	20 years	Female	Left lower limb weakness and balance disturbances	Hyperintensity in subcortical nuclei of the left hemisphere and in the matter next to the anterior horn of the right ventricle	EBV infection	Cyclosporine, etoposide and dexamethasone	Remission
Pan et al []¹³	10 months	Female	High fever of unknown origin, convulsions, jaundice, pancytopenia, coagulopathy, hepatosplenomegaly	–	EBV infection	Etoposide, steroids, intrathecal methotrexate, cyclosporine	Complete remission
Drago et al []¹⁴	16 years	Female	Fever, joint pain, recurrent respiratory infections, immune deficiency	–	Recurrent viral infections	Etanercept, high doses of immunoglobulin	Complete remission
Woodward et al []¹⁵	59 years	Female	Disorientation, bilateral lower limb weakness, mental status fluctuations, severe abulia, paresis, paraplegia with sensory level in the chest	Trace intraventricular hemorrhage, increased signal within the sulci in the parieto-occipital lobes as well as hyperintensities within the periventricular white matter, non-compressive subarachnoid hemorrhage (SAH) at the level of T6–T10	Ehrlichiosis	Dexamethasone, etoposide	Partial remission with residual paraplegia
Harburg et al []¹⁶	17 years	Male	Lower-extremity weakness, fatigue, headache, paraparesis	–	EBV infection (?) Familial	Immunoglobulins, rituximab, etoposide, cyclosporine A, methotrexate, dexamethasone, allogenic stem cell transplant	Death
Magaki et al []¹⁷	41 years	Male	Fever, night sweats, weight loss, generalized fatigue	Hyperintensity in multifocal, gyriform cortical, subtle enhancement	EBV infection	Symptomatic	Death
Gratton et al []¹⁸	38 years	Male	Disorientation, somnolence, spastic tetraparesis, seizure, cognitive slowing	Increased signal in the basal ganglia and patchy periventricular and subcortical white matter hyperintensities	Ankylosing spondylitis, SLE	Cyclosporine, dexamethasone, etoposide	Complete remission
Gratton et al []¹⁸	62 years	Female	Encephalopathy, seizure	Hyperintensity in the basal ganglia, external capsule, periventricular white matter	Rheumatoid arthritis, EBV infection	Dexamethasone, etoposide, rituximab	Partial remission
Gratton et al []¹⁸	21 years	Female	Seizure	Hyperintensity in the basal ganglia, external capsule, cortex, and subcortical white matter	Malaria	Dexamethasone, cladribine, immunoglobulins	Death
Pastula et al []¹⁹	55 years	Male	Disequilibrium, gait unsteadiness, left foot drop, right-hand paresthesia, seizure	Hyperintensity in supra- and infratentorial areas involving the cortex and juxtacortical white matter	Unknown	Methylprednisolone	Death
Gold et al []²⁰	63 years	Male	Seizure, left hemiparesis, deteriorating mental status	Hyperintensity in the right frontal and parietal cortical regions and throughout the subcortex	Rheumatoid arthritis	Dexamethasone, cyclosporine, etanercept	Complete remission
Gold et al []²⁰	27 years	Male	Status epilepticus	Non-specific signal intensities in the frontal subcortical white matter	Unknown	Etoposide, corticosteroids, methotrexate	Death
Anderson et al []²¹	56 years	Male	Encephalopathy	Hyperintensity in bi-hemispheric white matter and basal ganglia	Unknown	Steroids, chemotherapy	Death
Shah et al []²²	25 years	Male	Confusion, seizure	Diffuse white matter signal in the right temporal, occipital and parietal lobes, edema	Cutaneous T-cell lymphoma	Alemtuzumab, etoposide, dexamethasone, methotrexate	Remission
Algahtani et al []²³	20 years	Male	Headache, decrease in vision, seizure	Multiple confluent white matter demyelinating lesions in both cerebral hemispheres (mostly involving the parietal and occipital lobes), corpus callosum, cerebellar hemispheres, dorsal pons, brain volume loss	Familial	Steroids, cyclosporin A, dexamethasone, etoposide, allogeneic stem cell transplantation	Unknown
Han et al []²⁴	52 years	Female	Alert, abnormal behavior, seizure	Hyperintensity in bilateral deep white matter	Infection	Doxorubicin, etoposide, methylprednisolone	Complete remission
Verma et al []²⁵	68 years	Female	Confused, forgetful, seizure	Hyperintensity in the right hemisphere, medial left occipital lobe, and pons	Large B-cell lymphoma	Dexamethasone, etoposide, methotrexate hydrocortisone, rituximab, cyclophosphamide, doxorubicin, prednisone	Complete remission
Radmanesh et al []²⁶	46 years	Female	Spasticity, hyperreflexia and myoclonus	Thalamic hypodensitiy, diffuse, severe edema, innumerable microscopic and small hemorrhages	Still’s disease	Dexamethasone, etoposide	Death
Radmanesh et al []²⁶	44 years	Female	Altered consciousness	Innumerable microscopic and small hemorrhages	Unknown	Dexamethasone, etoposide	Complete remission
Oppegard et al []²⁷	70 years	Female	Encephalopathy, visual hallucinations, diplopia, gaze	Hyperintensity in the pons and supratentorial lesions	Large B-cell lymphoma	Antibiotics, etoposide, methotrexate, R-CHOP chemotherapy	Unknown
Hiraldo et al []²⁸	43 years	Male	Disturbance of consciousness, cognitive and language impairment, left limbs hemiparesis, seizure	Leptomeningeal enhancement and nodular enhancement in right basal ganglia and subcortical white matter	Unknown	Antibiotics, acyclovir, steroids, anakinra	Complete remission
Lehrer et al []²⁹	32 years	Female	Headache, irritability, right leg weakness, urinary hesitancy	Hyperintensity in the basal ganglia, lateral ventricles, and corona radiata	Anaplastic lymphoma	methotrexate, anakinra, dexamethasone, CHOP chemotherapy	Remission
Southam et al []³⁰	22 years	Female	Diplopia, hemianesthesia, hemiparesis, incoordination, headache, tremor	Hyperintensity in the cerebellar hemispheres and white matter with leptomeningeal involvement	Familial	Dexamethasone, etoposide, methotrexate	Death
Southam et al []³⁰	30 years	Male	Dysarthria, hemiplegia, cognitive decline	Hemorrhage involving unilateral thalamus and midbrain and innumerable micro-hemorrhage	Familial	Cyclosporin A, dexamethasone, etoposide, methotrexate, rituximab	Death
Southam et al []³⁰	17 years	Male	Dysarthria, ataxia, diplopia, hemiplegia	Bilateral hyperintensities in parietal lobes, supratentorial white matter hyperintensities	Familial	Dexamethasone, cyclosporine, allogeneic stem cell transplantation	Death
Wang et al []³¹	14 years	Male	Intermittent dizziness, blurred vision, lower limb weakness, unstable walking	Abnormal signals in the bilateral cerebellar hemisphere and vermis, right occipital lobe, and bilateral basal ganglia	Familial	Dexamethasone, methotrexate, allogenic stem cells transplantation	Improvement
Chen et al []³²	27 years	Male	Impaired consciousness, and generalized seizures	Increased vessel enhancement in the cerebral sulci and bilateral dura thickening	Unknown	Pulse of steroids, plasmapheresis	Death
Haanpää et al []³³	38 years	Male	Super-refractory status epilepticus	Left temporal arachnoid cyst	Infection	Midazolam, levetiracetam, steroids, hemodialysis, propofol, thiopental, immunoglobulins	Death
Huang et al []³⁴	37 years	Female	Debilitating headache, dizziness and drowsiness, fever, seizures, cognitive dysfunction	High signal intensity in the cortex of the left occipital lobe and enlarged cerebral sulcus vessels	Diffuse large B-cell lymphoma	Steroids, immunoglobulins, R-CHOP, pirarubicin, cytarabine	Improvement
Huang et al []³⁴	63 years	Female	Left-sided facial convulsions, salivation from the corner of the mouth, seizures, cognitive dysfunction	Multiple abnormal signals in the bilateral temporal insula	EBV-positive lymphoma	Steroids, immunoglobulins, antiepileptics, etoposide, dexamethasone, R-CHOP	Remission
Huang et al []³⁴	36 years	Female	Mental and behavioral abnormalities after experiencing a cold, with blurred vision, decreased comprehension, calculation, orientation, memory, and judgment, slowed movements, tense limbs, increased salivation, recurrent fever, convulsions	Spots of abnormal signaling in the right radial crown	Severe infection	Antiepileptics, anti-infection agents, steroids, immunoglobulin, immunoadsorption, rituximab, antifungal therapy, including vancomycin, cefoperazone sodium, tazobactam sodium, posaconazole, etoposide	Death
Kong et al []³⁵	19 years	Male	Facial paresthesias and mild cognitive and thinking abnormalities	Multiple high-density nodules and masses with peripheral edema in bilateral semiovale center, corpus callosum, bilateral paraventricular areas, right frontal lobe, and left cerebellar hemisphere		Pagaspargase, toripalimab, methotrexate, vincristine, etoposide, chidamide, dexamethasone, etoposide, doxorubicin liposome, haploidentical hematopoietic transplantation	Remission
CHOP – cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone [chemotherapy regimen]; EBV – Epstein-Barr virus; R-CHOP – rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), and prednisone [chemotherapy regimen]; SLE – systemic lupus erythematosus.

Back to the Article

Adult Hemophagocytic Lymphohistiocytosis (HLH) with Neurological Involvement: Diagnostic Complexities – A Case Report and Literature Review

Your Privacy