Table 1
Summary of Clinical and Investigative Features in 152 Lymphoid Malignancy Associated Movement Disorder Cases.
| Age | Mean: 51 Median: 56 Range: 1–86 IQR: 33 |
| Sex | Female (F): 68 (44.7%) Male (M): 84 (55.3%) |
| Continent-wise Distribution of Reported Cases (n = 145) | Europe: 46 (31.7%) Asia: 46 (31.7%) North America: 42 (29.0%) Oceania: 5 (3.4%) South America: 4 (2.8%) Africa: 1 (0.7%) |
| Specific lymphoid malignancy diagnosis as per WHO classification | Mature B-cell Neoplasms: 82 (53.9%)
Classical Hodgkin Lymphoma (all subtypes): 35 Nodular sclerosis Mixed cellularity Lymphocyte-depleted NOS/Stage IIB, III, IV-B Nodular Lymphocyte-Predominant HL (NLPHL): 1 Precursor Lymphoid Neoplasms: 17 (11.2%) B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (B-ALL/LBL): 17 Ph+ Ph– FAB L1/L2 Childhood ALL survivors Post-HSCT ALL Chronic Lymphocytic Leukemia/SLL: 7 (4.6%) CLL (longstanding/treated/with PNS) SLL (Stage IV-B) Other/Overlap Entities: 5 (3.3%) Gray zone lymphoma (B-cell/Hodgkin overlap) Composite lymphoma (Hodgkin + B-LPD) CML → ALL transformation Thymoma-associated SPS + remote NHL No active lymphoma (stiff-limb syndrome) |
| Staging of the disease | CNS-only disease: 36 (23.7%)Systemic disease with CNS involvement: 58 (38.2%)Systemic disease without CNS involvement: 19 (12.5%)Relapsed/refractory disease: 22 (14.5%)Post-transplant states: 12 (7.9%)Not staged/insufficient information: 25 (16.4%) |
| Molecular Markers | Lymphoma-defining immunophenotype: 108 (71.1%) (B-cell, T-cell, NK-cell, HL, ALCL markers showing definite lymphoma biology) Paraneoplastic/autoimmune antibodies: 18 (11.8%) Molecular/cytogenetic abnormalities: 14 (9.2%) Not reported/insufficient information: 12 (7.9%) |
| CNS Involvement | Direct CNS involvement (tumor infiltration, lymphoma, leukemia, metastasis): 51(33.6%) Paraneoplastic/autoimmune CNS involvement (antibody-mediated, immune): 46 (30.3%) No CNS involvement/other non-tumor causes (drug toxicity, metabolic, infection, PML, radiation, normal): 55 (36.1%) |
| Spectrum of Movement Disorders (Many Cases Had Multiple Movement Disorders) | Cerebellar ataxia/cerebellar syndrome (all forms): 84 (55.3%) Parkinsonism (all forms): 28 (18.4%) Chorea/choreoathetosis/hemichorea:18 (11.8%) Myoclonus (all types): 14 (9.2%) Dystonia (all forms): 11 (7.2%) Tremor (action, postural, palatal, oculo-palatal): 7 (4.6%) Dyskinesias (oro-facial, limb, paroxysmal, acute): 7 (4.6%) Stiff-person spectrum (SPS/stiff-limb/PERM): 6 (3.9%) Opsoclonus–myoclonus–ataxia (OMA): 4 (2.6%) Tic disorder: 1 (0.7%) Other rare/mixed syndromes (perseverative behaviour, myorhythmia, etc.): 2 (1.3%) |
| Associated Neurological Manifestations | Cognitive impairment/encephalopathy: 48 (31.6%) Cranial nerve involvement: 42 (27.6%) Cerebellar signs (non-movement): 39 (25.7%) Motor weakness/hemiparesis: 28 (18.4%) Bulbar dysfunction: 24 (15.8%) Sensory loss: 23 (15.1%) Headache/raised ICP signs: 21 (13.8%) Speech/language disturbance (aphasia/dysphasia): 18 (11.8%) Behavioral/psychiatric symptoms: 12 (7.9%) Seizures: 14 (9.2%) Altered gait (non-ataxic): 19 (12.5%) Vertigo (isolated): 9 (5.9%) Brainstem signs: 10 (6.6%) Autonomic dysfunction: 7 (4.6%) |
| Onset of Movement Disorders | Subacute: 82 (53.9%) Acute: 27 (17.8%) Chronic: 21 (13.8%) Acute–subacute: 12 (7.9%) Treatment-triggered: 10 (6.6%) |
| CSF Findings (Each case assigned to only ONE highest-significance group) | Normal/near-normal CSF: 46 (30.3%) Lymphocytic pleocytosis ± high protein (Inflammatory CSF without malignant cells): 54 (35.5%) Malignant cells/clonal B-cells/definite CNS lymphoma:11 (7.2%) Oligoclonal bands positive/intrathecal IgG synthesis:18 (11.8%) Infection-related positivity (JCV, EBV, viral PCR, etc.): 6 (3.9%) High protein only (albuminocytologic dissociation/barrier dysfunction): 7 (4.6%) CSF not done/not reported/insufficient information: 10 (6.6%) |
| Neuroimaging Findings | Normal neuroimaging: 41 (27.0%) Cerebellar atrophy/cerebellar structural abnormalities: 22 (14.5%) Basal ganglia/thalamus/brainstem lesions (including caudate, putamen, GP, thalamus, SN, subthalamic nucleus, peduncles): 28 (18.4%) White-matter hyperintensities (T2/FLAIR) leukoencephalopathy: 32 (21.1%) Enhancing mass lesions (tumor, lymphoma, metastasis, hemorrhagic or necrotic): 19 (12.5%) Leptomeningeal disease/meningeal enhancement: 6 (3.9%) Spinal cord involvement (intramedullary, enhancement, extradural tumor): 4 (2.6%) Inferior olive hypertrophy/HOD: 4 (2.6%) Hydrocephalus/mass-effect related ventricular dilation: 3 (2.0%) Subdural hematoma/hygroma: 3 (2.0%) Other rare findings (MRS metabolic change, isolated cortical atrophy, etc.): 3 (2.0%) |
| PET Findings | Systemic FDG-avid lymphadenopathy/systemic lymphoma activity present: 38 (25.0%) No systemic disease on imaging (normal or non-avid): 29 (19.1%) CNS-only PET/SPECT abnormality (cerebellar hyper/hypometabolism; BG uptake): 8 (5.3%) Infection/inflammation/non-malignant extracranial findings (pneumonitis, cardiomyopathy, gastric ulcers, nonspecific rib uptake, chemical toxicity): 6 (3.9%) Organ-specific lesions without systemic lymphoma (lung nodules, gastric lesion, vallecular mass, etc.): 7 (4.6%) Mixed systemic abnormalities (thoracic/abdominal nodes + other lesions): 5 (3.3%) Negative initial imaging → later new systemic disease detected (Delayed PET positivity/new nodal or pulmonary lesions): 5 (3.3%) Imaging performed but inconclusive: 6 (3.9%) No PET-CT/CT/systemic imaging performed or not reported: 48 (31.6%) |
| Treatment Given | Systemic chemotherapy: 83 (54.6%) High-dose methotrexate–based therapy: 41 (27.0%) Rituximab-containing regimens: 57 (37.5%) Radiotherapy: 38 (25.0%) Stem-cell transplant: 29 (19.1%) Immunotherapy/biologics: 17 (11.2%) Steroids/immunosuppression only: 21 (13.8%) No treatment/watch-and-wait: 12 (7.9%) Surgery only: 7 (4.6%) Targeted therapy Rituximab: 29 (19%) Brentuximab vedotin: 2 (1%) Pembrolizumab: 1 (1%) Alemtuzumab: 1 (1%) Dasatinib: 2 (1%) None: 117 (77%) HSCT/BMT No HSCT: 132 (86.8%) Autologous HSCT: 8 (5.3%) Allogeneic HSCT: 6 (3.9%) Both Auto + Allo: 1 (0.7%) BMT (unspecified): 5 (3.3%) Other medical treatments Steroids: 41 (27%) IVIG: 34 (22%) Plasmapheresis: 12 (8%) Levodopa/dopaminergic drugs: 29 (19%) Benzodiazepines: 24 (16%) Antiepileptics (LEV/VAL/CBZ/GABA): 31 (20%) Antipsychotics (HAL/TBZ): 17 (11%) Anticholinergics (trihexyphenidyl/benztropine): 9 (6%) Botulinum toxin: 1 (1%) Neurosurgery: 5 (3%) Supportive/rehab only: 48 (32%) No treatment reported: 39 (26%) |
| Response to treatment | Marked/complete improvement: 63 (41%) Partial improvement: 42 (28%) Stabilization only: 18 (12%) No improvement/worsening: 29 (19%) |
| Follow up Period | <1 month: 20 (13.2%) 1–3 months: 24 (15.8%) 3–6 months: 28 (18.4%) 6–12 months: 30 (19.7%) 1–2 years: 25 (16.4%) 2–5 years: 17 (11.2%) >5 years: 8 (5.3%) |
| Proposed Mechanisms of Movement Disorders | Direct CNS infiltration: 41 (27%) Paraneoplastic/autoimmune: 52 (34%) Drug-induced toxicity: 26 (17%) Infectious (PML/viral/fungal): 9 (6%) Radiation-related toxicity: 7 (5%) Metabolic/nutritional: 4 (2.6%) Vascular/ischemic: 5 (3.3%) Structural/degenerative (HOD etc.): 5 (3.3%) Reversible functional: 3 (2%) |
[i] ABMT – Autologous Bone Marrow Transplant; ABVD – Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine; ACTH – Adrenocorticotropic Hormone; ALL – Acute Lymphoblastic Leukemia; allo-HSCT – Allogeneic Hematopoietic Stem-Cell Transplant; Ara-C – Cytarabine; ASCT – Autologous Stem-Cell Transplant; BG – Basal Ganglia; BMT – Bone Marrow Transplant; B-NHL – B-cell Non-Hodgkin Lymphoma; B-ALL/LBL – B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma; CBZ – Carbamazepine; cGVHD – Chronic Graft-Versus-Host Disease; CLL – Chronic Lymphocytic Leukemia; CNS – Central Nervous System; COEP/OCEP – Cyclophosphamide, Vincristine, Etoposide, Prednisolone/Oncovin, Cyclophosphamide, Etoposide, Prednisolone; COP – Cyclophosphamide, Vincristine, Prednisone; CRMP-5 – Collapsin Response Mediator Protein-5; CyA – Cyclosporine A; DLBCL – Diffuse Large B-Cell Lymphoma; ENKL – Extranodal NK/T-Cell Lymphoma; EVAP – Etoposide, Vinblastine, Adriamycin, Prednisone; FAB – French-American-British Classification; FLAIR – Fluid-Attenuated Inversion Recovery; FL – Follicular Lymphoma; FOG – Freezing of Gait; GABA – Gamma-Aminobutyric Acid; GAD – Glutamic Acid Decarboxylase; GP – Globus Pallidus; GZL – Gray Zone Lymphoma; HOD – Hypertrophic Olivary Degeneration; HL – Hodgkin Lymphoma; HRCT – High-Resolution Computed Tomography; HSCT – Hematopoietic Stem-Cell Transplant; IQR – Interquartile Range; IT-MTX – Intrathecal Methotrexate; IVLBCL – Intravascular Large B-Cell Lymphoma; IVIG – Intravenous Immunoglobulin; JCV – John Cunningham Virus; LEV – Levetiracetam; LPC – Lymphoplasmacytic Cells; MALT – Mucosa-Associated Lymphoid Tissue; MF – Mycosis Fungoides; MMF – Mycophenolate Mofetil; MRS – Magnetic Resonance Spectroscopy; MTX – Methotrexate; MOPP – Mustine, Oncovin, Procarbazine, Prednisone; MRI – Magnetic Resonance Imaging; NAD – No Abnormality Detected; NHL – Non-Hodgkin Lymphoma; NK/T – Natural Killer/T-Cell; NOS – Not Otherwise Specified; OMA – Opsoclonus–Myoclonus–Ataxia; PCD – Paraneoplastic Cerebellar Degeneration; PCR – Polymerase Chain Reaction; PCNSL – Primary CNS Lymphoma; PCP – Pneumocystis Pneumonia; PD-1 – Programmed Cell Death Protein 1; PERM – Progressive Encephalomyelitis with Rigidity and Myoclonus; PET-CT – Positron Emission Tomography–Computed Tomography; Ph+ – Philadelphia Chromosome Positive; Ph– – Philadelphia Chromosome Negative; PML – Progressive Multifocal Leukoencephalopathy; PTCL – Peripheral T-Cell Lymphoma; R-CHOP – Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone; R-CVP – Rituximab, Cyclophosphamide, Vincristine, Prednisone; R-EPOCH – Rituximab, Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin; R-MPV – Rituximab, Methotrexate, Procarbazine, Vincristine; SLL – Small Lymphocytic Lymphoma; SMZL – Splenic Marginal Zone Lymphoma; SN – Substantia Nigra; SPS – Stiff-Person Syndrome; SUV – Standardized Uptake Value; TBZ – Tetrabenazine; TMP-SMX – Trimethoprim–Sulfamethoxazole; T-FH – T-Follicular Helper Cell; VP Shunt – Ventriculoperitoneal Shunt; WM – Waldenström Macroglobulinemia; WBRT – Whole-Brain Radiotherapy; WHO – World Health Organization; WMH – White-Matter Hyperintensity.
Figure 1
The PRISMA flow diagram summarizing the study selection process. It shows the number of records identified, screened, assessed for eligibility, and finally included in the review.
Table 2
Summary of 78 Reported Cases of Movement Disorders in Myeloid Malignancies.
| Age | NA: 1 Mean: 57.1 Median: 62 Range: 8–96 IQR: 31 |
| Sex | Male (M): 36 (46.1%) Female (F): 41 (52.6%) Not available (NA): 1 (1.3%) |
| Continent-wise Distribution of Reported Cases (n = 74) | Asia (incl. Middle East & Asian Russia): 31 (40.8%) North America: 23 (30.3%) Europe: 18 (23.7%) South America: 2 (2.6%) Oceania: 1 (1.3%) Africa: 1 (1.3%) |
| Specific Myeloid Malignancy Diagnosis as per WHO Classification | Myeloproliferative Neoplasms (MPN): 46 (59.0%)
Acute Myeloid Leukemia (AML): 22 (28.2%) Myelodysplastic Syndrome (MDS): 2 (2.5%) MDS/MPN Overlap: 1 (1.3%) |
| Staging of the disease | Newly diagnosed: 27 (34.6%) Long-standing/chronic: 20 (25.6%) Post-HSCT: 17 (21.8%) During therapy: 12 (15.4%) Relapse/deterioration: 2 (2.6%) |
| Molecular Markers | JAK2-positive: 38 (48.7%) BCR-ABL–positive: 4 (5.1%) AML-mutation profiles: 6 (7.7%) No molecular data (pre-JAK2/not reported): 20 (25.6%) Other/HSCT-related/mixed: 10 (12.8%) |
| CNS Involvement | No CNS leukemia: 56 (71.8%) Drug-induced neurotoxicity: 14 (17.9%) CNS infection: 3 (3.8%)
CNS-GVHD: 3 (3.8%) True CNS leukemia: 2 (2.6%) |
| Spectrum of Movement Disorders (Many Cases Had Multiple Movement Disorders) | Generalized chorea: 32 (41.0%) Hemichorea/hemiballismus: 14 (17.9%) Cerebellar ataxia/cerebellar syndrome: 15 (19.2%) Parkinsonism: 7 (9.0%) Myoclonus/myoclonic epilepsy/OMS: 6 (7.7%) Dystonia: 4 (5.1%) Other rare hyperkinetic movement disorders: 3 (3.8%)
Mixed (complex) presentations: 2 (2.6%) |
| Associated Neurological Manifestations | Cognitive/behavioral: 18 (23.1%) Speech impairment: 16 (20.5%) Sensory/neuropathy: 10 (12.8%) Autonomic dysfunction: 8 (10.3%) Cerebellar/vestibular-associated: 9 (11.5%) Weakness/pyramidal: 7 (9.0%) Miscellaneous systemic neurologic: 10 (12.8%) |
| Onset of Movement Disorders | Acute: 20 (25.6%) Subacute: 25 (32.1%) Chronic/Gradual: 15 (19.2%) Treatment-related: 18 (23.1%) |
| CSF Findings (Each case assigned to only ONE highest-significance group) | Normal CSF: 39 (50.0%) CSF not done/not reported: 29 (37.2%) Mild abnormal CSF: 10 (12.8%) Infectious CSF positivity: 3 (3.8%) CNS leukemic meningitis: 1 (1.3%) |
| Neuroimaging Findings | Normal neuroimaging: 27 (34.6%) Chronic ischemia/microangiopathy/atrophy: 17 (21.8%) Acute infarcts/vascular lesions: 9 (11.5%) Basal ganglia/deep gray abnormalities: 9 (11.5%) Cerebellar lesions: 5 (6.4%) Multifocal/diffuse WM lesions: 6 (7.7%) Ring-enhancing/infective–inflammatory lesions: 2 (2.6%) Hemorrhagic lesions: 2 (2.6%) CNS leukemic infiltration: 1 (1.3%) |
| PET Findings | PET/SPECT not done/not available: 52 (66.7%) Normal PET/SPECT/CT-CAP: 12 (15.4%) Abnormal PET/SPECT: 6 (7.7%)
Perfusion/venous abnormalities: 3 (3.8%) Structural CT/MRI mentioned in PET section: 5 (6.4%) |
| Treatment Given | Phlebotomy/venesection ± aspirin: 27 (34.6%) Hydroxyurea-based therapy: 20 (25.6%) HSCT/BMT/immunosuppression: 14 (17.9%) TKIs: 6 (7.7%) AML multi-agent chemotherapy: 5 (6.4%) APL therapy (ATRA/ATO): 2 (2.6%) Immunomodulators (thalidomide/lenalidomide): 3 (3.8%) Supportive only: 1 (1.3%) Targeted Therapy: 2 (2.6%) Protein kinase inhibitor Azacitidine + azathioprine (stopped) HSCT Allogeneic HSCT: 10 (12.8%) Autologous HSCT: 1 (1.3%) HSCT × 2: 1 (1.3%) No HSCT: 66 (84.6%) Medical Therapy
|
| Response to treatment | Complete resolution: 23 (29.5%) Marked improvement: 21 (26.9%) Partial improvement: 17 (21.8%) Poor/minimal/no improvement: 6 (7.7%) Improvement after hematologic correction: 7 (9.0%) Supportive only (non-specific): 4 (5.1%) |
| Follow up Period | <1 month: 7 (9.0%) 1–3 months: 15 (19.2%) 3–6 months: 18 (23.1%) 6–12 months: 14 (17.9%) 1–2 years: 10 (12.8%) 2–5 years: 7 (9.0%) ≥5 years: 3 (3.8%) Not stated: 4 (5.1%) |
| Proposed Mechanisms of Movement Disorders | Hyperviscosity-related: 36 (46.1%) Drug-induced toxicity: 17 (21.8%) Immune-mediated/GVHD: 10 (12.8%) JAK2-specific (non-hyperviscosity): 4 (5.1%) Infection-related: 5 (6.4%) Hemorrhagic/vascular fragility: 2 (2.6%) Degenerative/structural: 2 (2.6%) Metallotoxic: 1 (1.3%) Unclear/not stated: 1 (1.3%) |
[i] AML — Acute Myeloid Leukemia; APML — Acute Promyelocytic Leukemia; ATRA — All-trans Retinoic Acid; ATO — Arsenic Trioxide; BCR-ABL — Breakpoint Cluster Region–Abelson Fusion Gene; BMT — Bone Marrow Transplant; CAP — Chest–Abdomen–Pelvis; CML — Chronic Myeloid Leukemia; CNS — Central Nervous System; CSF — Cerebrospinal Fluid; CT — Computed Tomography; ET — Essential Thrombocythemia; FDG-PET — Fluorodeoxyglucose Positron Emission Tomography; F — Female; GVHD — Graft-Versus-Host Disease; HSCT — Hematopoietic Stem Cell Transplantation; HU — Hydroxyurea; IQR — Interquartile Range; IVIG — Intravenous Immunoglobulin; JAK2 — Janus Kinase 2; M — Male; MDS — Myelodysplastic Syndrome; MPN — Myeloproliferative Neoplasm; MRI — Magnetic Resonance Imaging; NA — Not Available; OMS — Opsoclonus–Myoclonus Syndrome; PET — Positron Emission Tomography; PLEX — Plasma Exchange; PMF — Primary Myelofibrosis; PML — Progressive Multifocal Leukoencephalopathy; PV — Polycythemia Vera; RTX — Rituximab; SPECT — Single-Photon Emission Computed Tomography; TKI — Tyrosine Kinase Inhibitor; VNS — Vagus Nerve Stimulation; WM — White Matter.
Table 3
Summary of 22 Cases of Myeloma-Associated Movement Disorders.
| Age | Mean: 60.6 Median: 65 Mode: 65 Range: 31–78 IQR: 13 |
| Sex | Male: 10 (45.45%) Female: 12 (54.55%) |
| Continent-wise Distribution of Reported Cases (n = 20) | North America: 9 (45%) Asia: 6 (30%) Europe: 5 (25%) |
| Specific hematological malignancy diagnosis as per WHO classification | Multiple Myeloma: 19 (86.4%) Smoldering Multiple Myeloma: 1 (4.5%) Plasmacytoma: 1 (4.5%) IgM MGUS → MM: 1 (4.5%) |
| Staging of the disease | Staged (ISS/R-ISS available): 7 (31.8%) Progressive/Relapsed/Refractory: 8 (36.4%) Long remission (post-BMT): 1 (4.5%) Systemic involvement: 1 (4.5%) Not reported/Not stated: 5 (22.7%) |
| Molecular Markers | Cytogenetic/FISH abnormalities: 7 (31.8%) Monoclonal protein abnormalities: 9 (40.9%) Not reported: 6 (27.3%) |
| CNS Involvement | No CNS infiltration: 12 (54.5%) Autoimmune/Paraneoplastic: 5 (22.7%) Infectious: 2 (9.1%) Other CNS diseases (leukoencephalopathy/neurodegenerative): 3 (13.6%) |
| Spectrum of Movement Disorders (Many Cases Had Multiple Movement Disorders) | Parkinsonism:10 (45.5%) Cerebellar syndromes/Ataxia: 6 (27.3%) Tremor disorders: 4(18.2%) Other movement disorders : 6 (27.3%) (List of all individual “other” disorders): Tardive dyskinesia–like extrapyramidal syndrome (EPS) Multifocal myoclonus Restless legs syndrome (RLS) Stiff-person syndrome (SPS) Involuntary movements (not otherwise specified) Dystonia |
| Associated Neurological Manifestations | Cognitive/Encephalopathic: 7 (31.8%) Sensory/Peripheral neuropathy: 6 (27.3%) Cranial nerve involvement: 3 (13.6%) Pyramidal signs: 3 (13.6%) Myoclonic/stiffness episodes: 1 (4.5%) Hydrocephalus/mass effect: 1 (4.5%) None: 2 (9.1%) |
| Onset of Movement Disorders | Long latency (>2 years): 10 (47.6%) Intermediate latency (1–2 years): 5 (23.8%) Short latency (<6 months): 4 (19.0%) Not applicable: 1 (4.8%) Symptoms preceded MM diagnosis: 3 cases |
| CSF Findings | Normal: 7 (31.8%) Abnormal (non-infectious): 4 (18.2%) Infectious: 2 (9.1%) Negative panels: 3 (13.6%) Not done/Not reported: 6 (27.3%) |
| Neuroimaging Findings | Normal: 7 (31.8%) Cerebellar pathology: 5 (22.7%) White matter changes: 3 (13.6%) Cortical ribboning/degenerative: 2 (9.1%) Not done/Not reported: 4 (18.2%) |
| PET Findings | Normal/Negative PET-CT: 4 (18.2%) Other abnormality (non-MM): 1 (4.5%) Not done/Not performed: 17 (77.3%) |
| Treatment Given | CAR-T therapy: 5 (22.7%) Bortezomib-based regimens: 5 (22.7%) Lenalidomide-based regimens: 4 (18.2%) Melphalan-based regimens: 4 (18.2%) Radiotherapy/Surgery: 2 (9.1%) Multiple prior regimens: 1 (4.5%) Supportive/Referred: 1 (4.5%) Targeted Therapy CAR-T: 2 (9.1%) Ruxolitinib: 2 (9.1%) Bortezomib: 2 (9.1%) IMiDs: 3 (13.6%) Interferon-α: 1 (4.5%) None/Not reported: 11 (50.0%) HSCT Autologous HSCT: 8 (36.4%) Neurological Treatment Immunotherapy (IVIG/steroids/anakinra/cyclophosphamide): 7 (31.8%) Movement-disorder drugs (levodopa, amantadine, primidone, propranolol, clonazepam, DBS/thalamotomy): 6 (27.3%) Drug withdrawal/dose reduction (stopping LEN/thalidomide/pregabalin, TMP-SMX reduction): 4 (18.2%) Supportive care only: 3 (13.6%) Neurosurgery (decompression/ventriculostomy): 2 (9.1%) Other symptomatic drugs (amitriptyline, piracetam, prednisolone): 2 (9.1%) |
| Response to Treatment | Complete resolution: 6 (27.3%) Marked improvement: 7 (31.8%) Partial improvement: 5 (22.7%) Minimal benefit: 1 (4.5%) No improvement/progression: 3 (13.6%) |
| Follow up Period | <3 months: 5 (22.7%) 3–12 months: 7 (31.8%) >1 year: 8 (36.4%) Not reported/not stated: 2 (9.1%) |
| Proposed Mechanisms of Movement Disorders | Drug-induced: 7 (31.8%) Immune/cytokine-mediated: 6 (27.3%) Paraneoplastic/autoimmune: 5 (22.7%) Mass lesion: 1 (4.5%) Infectious: 1 (4.5%) Degenerative: 1 (4.5%) Metabolic/nutritional: 1 (4.5%) |
[i] BMT: Bone Marrow Transplantation; CAR-T: Chimeric Antigen Receptor T-cell therapy; CNS: Central Nervous System; CSF: Cerebrospinal Fluid; DBS: Deep Brain Stimulation; EPS: Extrapyramidal Syndrome; FISH: Fluorescence In Situ Hybridization; HSCT: Hematopoietic Stem Cell Transplantation; IgM MGUS: Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance; IMiDs: Immunomodulatory Drugs; IQR: Interquartile Range; ISS: International Staging System; IVIG: Intravenous Immunoglobulin; LEN: Lenalidomide; MM: Multiple Myeloma; PET-CT: Positron Emission Tomography–Computed Tomography; R-ISS: Revised International Staging System; RLS: Restless Legs Syndrome; SPS: Stiff-Person Syndrome; TMP-SMX: Trimethoprim-Sulfamethoxazole; WHO: World Health Organization.