Sensory ganglionopathy (SG) is a neurological syndrome that may be associated with paraneoplastic neurologic disorders (PNDs) and is characterized by primary degeneration of the dorsal root ganglia sensory neurons. 1 The preferred involvement of the vibratory and position sense can rarely cause pseudodystonic posturing and pseudoathetotic movements. 2
Small‐cell lung carcinoma (SCLC) is the most common malignant process associated with SG. 1 Anti‐Hu/ANNA‐1 antibodies are the most frequently related antineuronal autoantibodies whereas anti‐Amphiphysin antibodies have exceptionally been found in patients with paraneoplastic SG. 1 , 3 In most of the cases the neurologic symptoms precede the cancer diagnosis by weeks or months. 1
A 72‐year‐old man presented with a 2‐month history of weight loss and bilateral dorsal radicular pain in the dermatomal distribution of C8. Two months later he experienced progressive sensory loss and involuntary movements of the four limbs with progressive difficulty walking. Neurological examination revealed generalized areflexia with loss of vibration and position sense and decreased pain and temperature sensation in a stocking‐glove distribution in the four limbs. Furthermore, he exhibited pseudodystonic hands posturing and asymmetric athetosic movements of the four limbs that became more prominent with eye closure (Video 1, segment 1). He was not able to stand due to prominent sensory ataxia.
Video 1.
Segment one shows the patient at time of diagnosis with pseudodystonic posturing and pseudoatethosis in both arms. On finger‐to‐nose testing there is an important worsening with eye closure; segment two shows the patient 8 months after treatment. Stabilization of the involuntary movements and unassisted deambulation with a broad‐based gait are shown.
Nerve conduction studies showed absent sensory nerve action potentials in sural and median nerves bilaterally but motor conduction velocities were normal (Fig. 1B). CSF showed no pleocytosis, protein content slightly elevated (65 mg/dL) and normal glucose. Anti‐Hu/ANNA‐1 and anti‐Amphyphisin antibodies were positive in CSF (1:1 titer) and serum (1:100 titer) samples by indirect immunofluorescence (IF) on substrates of cerebellum and monkey intestinal tissue and confirmed by immunohistochemistry (IHC) on rat cerebellum and immunoblot with recombinant proteins. (Fig. 1A). PET‐CT scan showed a region of increased activity in the lung (Fig. 1C) and subsequent biopsy confirmed the diagnosis of SCLC.
FIG. 1.
Positive staining for anti‐Hu/ANNA‐1 and anti‐Amphyphisin antibodies of the cerebellum and the myenteric plexus of the gut in IF (kit commercial) (left) and IHC (right). Positive result in IB (EUROLINE Paraneoplastic neurological syndromes 12 Ag, Euroimmun) for anti‐Hu/ANNA‐1 and anti‐Amphyphisin antibodies in CSF (down) and serum (up) (A) absent left sural and median sensory nerve action potential (SNAP) in nerve conduction studies (B) Hypermetabolic nodule in whole‐body 18F‐FDG PET‐CT scan (arrowheads) (C).
The patient was treated with carboplatin and etoposide, radiotherapy as well as 0.4 g/kg intravenous immunoglobulins given over 5‐days at 4 months after symptom onset. At 8‐months follow up no recurrence of the tumor was reported, the involuntary movements stabilized and he was able to walk unassisted with ataxic gait (Video 1, segment 2).
Pseudoathetosis and pseudodystonia are uncommon hyperkinetic conditions where defective processing of proprioceptive information might lead to inability to integrate sensory and motor inputs. They involve predominantly the distal region of the limbs. The phenomenology is practically indistinguishable from choreoathetosis and dystonia but eye closure typically accentuates pseudoathetosis and pseudodystonia. This has been attributed to compensation of abnormal posture by the visual system. Furthermore, both types of movement disorders may coexist in SG and are usually confined to the region of sensory loss. 2
It is important to recognize them as they are usually associated with treatable and reversible disorders. 2 Besides, in rare cases of limbic encephalitis associated with anti‐Hu antibodies, choreoathetosis in the absence of other neurological signs and specific features on MRI can be found. 3
The coexistence of the two antibodies is atypical. The detection of more than one antibody against intracytoplasmic targets increases the likelihood of underlying malignancy and the lung carcinoma is one of the most common tumors involved. 4
Paraneoplastic SG is rarely responsive to steroids and other immunosuppressive therapies 4 but early treatment in moderately disabled patients may be beneficial. 5 However, treating the underlying cancer is the best way to halt progression and occasionally improve these paraneoplastic disorders. 5
This case highlights the importance of the correct characterization of the phenomenology of a movement disorder and reports an atypical clinical presentation of a rare neurologic disorder whose early identification is imperative, as they may herald underlying malignancy.
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
D.C.C.: 1A, 1B, 1C, 3A
A.V.A.: 1A, 1B, 1C
L.N.: 1A, 1B, 1C
R.R.G.: 1A, 1B, 1C
A.R.C.: 1A, 1B, 1C
J.R.M.: 3B
F.G.: 3B
Disclosures
Ethical Compliance Statement
The authors confirm that the approval of an institutional review board was not required for this work. The patient gave written consent for their personal or clinical details along with any identifying images to be published in this case report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.
Funding Sources and Conflicts of Interest
The authors declare that there are no funding sources or conflicts of interest relevant to this work.
Financial Disclosures for the Previous 12 Months
The authors declare that there are no additional disclosures to report.
Relevant disclosures and conflicts of interest are listed at the end of this article.
References
- 1. Amato A, Ropper A. Sensory ganglionopathy. N Engl J Med 2020;383:1657–1662. [DOI] [PubMed] [Google Scholar]
- 2. Berlot R, Bhatia K, Kojović M. Pseudodystonia: a new perspective on an old phenomenon. Parkinsonism Relat Disord 2019;62:44–50. [DOI] [PubMed] [Google Scholar]
- 3. Balint B, Vincent A, Meinck HM, Irani SR, Bhatia KP. Movement disorders with neuronal antibodies: syndromic approach, genetic parallels and pathophysiology. Brain 2018;141(1):13–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Horta ES, Lennon VA, Lachance DH, et al. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res 2014;20(14):3862–3869. [DOI] [PubMed] [Google Scholar]
- 5. Antoine J‐C, Robert‐Varvat F, Maisonobe T, et al. Identifying a therapeutic window in acute and subacute inflammatory sensory neuronopathies. J Neurol Sci 2016;361:187–191. [DOI] [PubMed] [Google Scholar]