Video 1
Patient 1 before and 1 Month after Initiation of Sodium Oxybate. Segment 1. Pre-sodium Oxybate. The examination in Segment 1 was performed 2 years after the onset of myoclonus. In this segment, myoclonus of the right leg, not present at rest, emerged when the patient stretched his leg out in a seated position. The myoclonus was prominent and mainly generated from the proximal leg. It was also present when standing and walking, and limited his ability to perform these activities. Bearing weight on the right foot (such as when standing on the right foot only) also triggered the myoclonus. After this visit, sodium oxybate was initiated and titrated up to 1.5 g twice a day. He had moderate benefit in dose-dependent fashion (not shown in the video at the lower dose). Segment 2. After Initiation of Sodium Oxybate. Segment 2 demonstrates Patient 1 after taking sodium oxybate for 1 month. The examination was performed 2 hours after the last dose. Myoclonic jerks of the right leg were moderately improved, and his ability to perform daily activities improved as well. He was able to walk independently, but still required his wife by his side due to fear of falling.
Video 2
Patient 2. Segment 1. The Examination Performed 1 Year after the Onset of Myoclonus (2 Years after the Diagnosis of Prostate Cancer). There was no myoclonus at rest. When he pushed the left thigh or extended the left knee against the examiner’s hand, prominent myoclonic jerks of the left leg emerged, especially from the proximal region around the hip joint. In one part of the video, he attempted to counter the jerks with his right leg. Upon arising from the chair and standing, myoclonic jerks of the left proximal leg became prominent leading to difficulty performing these activities and walking. Segment 2. Home Video Demonstrating Walking Immediately after Ingesting Two Glasses of Wine. Although walking with his walker, mild intermittent myoclonus of the left leg, mainly generated from the proximal region, was present; however, he was able to ambulate.
Table 1
Paraneoplastic Movement Disorders (PMD) in Prostate Cancer
| Reference | Phenomenology | Neurologic Syndrome | Age (yrs) | T Dx→Syn (yrs) | Tumor Stage | Tumor Histopath | Antibody (Site of Sample) | Treatment1 (Response) | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Our case (Patient 1), 2015 | Myoclonus—action, rt leg | Alcohol-responsive action myoclonus of the leg | 74 | 0.1 (3 wks) | Metastatic disease | Adeno | Unknown (serum and CSF) | IVMP (only transient benefit), IVIG (no); combination of Aza, LEV, CLZ (modest); sod oxybate (mod but less over time) | Initially stable but died 6 years after tumor diagnosis due to metastatic prostate cancer |
| Our case (Patient 2), 2015 | Myoclonus—action, lt leg | Alcohol-responsive action myoclonus of the leg | 76 | 1 | Diffuse bony metastasis | Adeno | Unknown(serum and CSF) | IVIG (no) | Stable neurologic sx |
| Baloh et al.17 | Myoclonus—face, masseter, pharyngeal and abdominal muscles | Brainstem syndrome—progressive loss of voluntary horizontal eye mvmts, dysphagia | 71 | 1 | Retroperitoneal pelvic mass contiguous with the prostate but no evidence of the tumor at other sites | Adeno | Unknown | Rx of the cancer by bil orchiectomy; CLZ and VPA (mod); PLEx (no) | Died of aspiration 3 years after tumor diagnosis |
| Baloh et al.17 | Continuous “muscle spasms”—rt face → both sides of face → pharyngeal and laryngeal muscles; mild gait ataxia | Brainstem syndrome—progressive loss of voluntary horizontal eye mvmts with relatively preserved vertical eye mvmts | 66 | 5 | Multiple pelvic lymphadenopathies but negative bone scan | Adeno | Unknown | DZP, VPA, baclofen LZP (modest with all); BoNT (“some relief”) | Ventilator-dependent; committed suicide 2 yrs after the onset |
| Modrego et al.18 | Myoclonus—generalized, developed later | Limbic encephalitis—disorientation, incoherent, non-fluent speech, unstable gait | 74 | −0.1 (1 mo) | Tumor invaded the prostatic capsule and spread to the rectal wall | Adeno | Unknown | Rx of the 1° tumor only | Died within 2–3 mo after the onset of limbic encephalitis, thought to be due to pneumonia |
| McLoughlin et al.19 | Ataxia—trunk | Cerebellar syndrome—rapidly progressive; pseudobulbar palsy, diplopia, transient migratory paresis of rt inferior rectus, rotatory nystagmus | 67 | 0.25 (3 mo) | T3NxM02 | “Poorly differentiated” | Unknown | Rx of the 1° tumor only | Stable cerebellar syndrome; progression of eye mvmts, thought to be “opsoclonus myoclonus” |
| Clouston et al. 20 | Ataxia—trunk and gait | Cerebellar syndrome—subacute, cerebellar atrophy on neuroimaging LEMS | 68 | 5 | Bony metastasis of the pelvis 2 years after the original tumor diagnosis, and later to L2 and L3 vertebral bodies | Originally adeno; small-cell ca on repeat biopsy 5 yrs later | Anti-VGCC (serum) | Recurrent cancer was treated with bil orchiectomy; corticosteroids, PLEx and guanidine HCl (all no) | Stable neurologic sx → rapid deterioration after hepatic metastasis 6 mo after the recurrence |
| Matschke et al.21 | Ataxia—limbs and gait | Cerebellar syndrome—unsteadiness, scanning dysarthria, nystagmus, saccadic dysmetria | 79 | −0.5 (6 mo) | T4N1M1 | Adeno with focal neuroendocrine differentiation | Anti-Yo (or anti-PCA1; serum and CSF) | None | Deteriorated rapidly and died of heart failure within one week after admission |
| Iorio et al.22 | Ataxia—gait | Cerebellar syndrome—cerebellar speech, nystagmus | 65 | 1.5 | T3aN0Mx | Adeno | Anti-mGluR1 (serum and CSF) | A course of IVIG (good) followed by oral prednisone (1 mg/kg/day) and monthly IVIG | Continued to improve on 9-mo follow up |
| Aliprandi et al.23 | Ataxia—limbs and gait | Cerebellar syndrome—progressive dysarthria | 80 | −0.8 (10 mo) | No evidence of extracapsular dissemination | Adeno | Anti-CV2/CRMP5 (serum) | IVIG (2 courses; on Dx [modest] and 3 mo later [no]); Rx of the 1° tumor with bicalutamide and tamoxifen | Remained markedly impaired despite the 2nd course of IVIG and no progression of underlying malignancy |
| Stern and Hulette24 | Ataxia—trunk | Limbic encephalitisCerebellar syndrome | 76 | −0.1 (1 mo) | N/A | Small cell ca with a minor component of adeno | Unknown (negative anti-Hu, anti-Ri and anti-Yo) | None | Died 12 days after admission |
| Jakobsen et al.25 | Ataxia | Limbic encephalitis—marked short-term memory impairment, personality changes, seizures, diplopia | 64 | −0.1 (1 mo) | T3bN0M0 | Adeno | Anti-Hu (ANNA-1; CSF) | IVMP (500 mg/day) for unknown duration, IVIG and PLEx; Rx of the 1° tumor incl palliative external beam XRT | Died 6 mo after the onset of limbic encephalitis |
| Berger et al.26 | Ataxia—gait | Recurrent brainstem syndrome—ophthalmoplegia, dysarthria, dysphagia, facial pruritus, facial numbness; leg stiffness | 59 | −0.7 (8 mo) | N/A but no evidence of metastasis | N/A | Intraneuronal Abs (serum and CSF) but unknown exact Ag | IVIG and IVMP (good initially, but no after the last recurrence; rituximab, IV CTX (no), PLEx (no) | Rituximab led to respiratory arrest; leukopenia from CTX |
Abbreviations: 1°, Primary; Abs, Antibodies; Adeno, Adenocarcinoma; Ag, Antigen; ANNA1, Anti-neuronal Nuclear Antibody Type 1; Aza, Azathioprine; bil, Bilateral; BoNT, Botulinum Toxin Injections; ca, Carcinoma; CLZ, Clonazepam; CSF, Cerebrospinal Fluid; CTX, xxx; CV2/CRMP5, Collapsing Response Mediator Protein 5; DZP, Diazepam; HCl, Hydrochloride; incl, Including; IVIG, Intravenous Immunoglobulin; IVMP, Intravenous Methylprednisolone; LEMS, Lambert–Eaton Myasthenic Syndrome; LEV, Levetiracetam; lt, Left; LZP, Lorazepam; mGluR1, Metabotropic Glutamate Receptor 1; mo, Month(s); mod, Moderate; mvmt(s), Movement(s); N/A, Not Applicable or Information Not Available; PCA1, Purkinje Cell Cytoplasmic Antibody Type 1; PLEx, Plasma Exchange; rt, Right; Rx, Treatment; sod, Sodium; sx, Symptoms; T Dx→Syn, Time from Tumor Diagnosis to the Onset of the Neurologic Syndromes; VGCC, Voltage-gated Calcium Channel; VPA, Valproic Acid; wks, Weeks; XRT, Radiation; yr(s), Year(s).
Table 1. This table demonstrates previously reported cases of PMDs in prostate cancer in the literature, with the addition of our cases (in dark pink). PMDs in prostate cancer are classified based on the phenomenology and neurologic syndromes. Among these cases, two phenomenologies have been reported including myoclonus (in shades of pink) and ataxia (in shades of green). Neurologic syndromes associated with myoclonus include isolated alcohol-responsive unilateral leg action myoclonus (in dark pink), brainstem syndromes (in light pink) and limbic encephalitis (in medium pink), whereas ataxia has been reported in cerebellar syndromes (in light green in the middle of the table), limbic encephalitis (dark green), and recurrent brainstem syndrome (in light green at the bottom).
In each case, age, time from tumor diagnosis to the onset of the neurologic syndromes (T Dx→Syn, in years), tumor stages, tumor histopathology (histopath), antibodies (with sites from which the samples were obtained), treatments (with responses in parentheses), and outcomes are listed. Note that a negative number of T Dx→Syn indicates that the neurologic syndromes were diagnosed before tumor diagnosis.