Diagnosis : Paraneoplastic polyneuropathy / sensory ganglionopathy.
PET scan sowed a lobulated 2 cm hypermetabolic lat. Rt. Middle lobe mass, subsequent biopsy of which showed a small cell lung carcinoma (SCLC). Panel of paraneoplastic autoantibodies showed seropositivity to anti-neuronal nuclear antibody-1 (ANNA-1) at 1:122,880 ( normal <1:240)
ANNA-1 (also known as ‘‘anti-Hu’’) is a marker of paraneoplastic autoimmunity associated with about 20% of patients with SCLC. Immunohistochemistry studies have demonstrated binding of ANNA-1 autoantibodies to nuclei of all neurons throughout the CNS and PNS, targeting a family of proteins known as Embryonic Lethal Abnormal Vision-Like or Hu (primarily HuD), which are RNA-binding proteins implicated in post-transcriptional regulation of RNA, and are expressed in both neurons and SCLC cells.
Peripheral neuropathy is a well known manifestation of ANNA-1 related syndrome, being seen in 60-95% of patients 1,2.Subacute sensory neuronopathy ( SSN) which results from destruction of sensory neuron cell bodies in dorsal root ganglia is the most frequent presentation. However, motor and autonomic neuron cell bodies can also be involved, rarely in isolation, and more commonly in association with SSN. The course of disease is usually subacute or progressive, and rarely acute and resembling GBS 2. EMG commonly shows sensory ganglionopathy (diffusely abnormal or absent SNAPs with normal motor responses and needle EMG), but motor neuropathy and demyelinating features were reported in about one fifth of the patients 2. As Hu antigen is not expressed in the peripheral nerves, peripheral neuropathy could be caused by autoimmunity to other nerve antigens 3. Other features of ANNA-1 related paraneoplastic syndrome include encephalomyelitis (~40% of cases) and autonomic neuropathy (~30%).
References
1. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu–associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine 1992;71(2):59-72.
2. Camdessanche JP, Antoine JC, Honnorat J, Vial C, Petiot P, Convers P, Michel D. Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients. Brain : a journal of neurology 2002;125(Pt 1):166-175.
3. Antoine JC, Mosnier JF, Honnorat J, Convers P, Absi L, Lapras J, Michel D. Paraneoplastic demyelinating neuropathy, subacute sensory neuropathy, and anti-Hu antibodies: clinicopathological study of an autopsy case. Muscle & nerve 1998;21(7):850-857.
Diagnosis : Paraneoplastic polyneuropathy / sensory ganglionopathy.
PET scan sowed a lobulated 2 cm hypermetabolic lat. Rt. Middle lobe mass, subsequent biopsy of which showed a small cell lung carcinoma (SCLC). Panel of paraneoplastic autoantibodies showed seropositivity to anti-neuronal nuclear antibody-1 (ANNA-1) at 1:122,880 ( normal <1:240)
ANNA-1 (also known as ‘‘anti-Hu’’) is a marker of paraneoplastic autoimmunity associated with about 20% of patients with SCLC. Immunohistochemistry studies have demonstrated binding of ANNA-1 autoantibodies to nuclei of all neurons throughout the CNS and PNS, targeting a family of proteins known as Embryonic Lethal Abnormal Vision-Like or Hu (primarily HuD), which are RNA-binding proteins implicated in post-transcriptional regulation of RNA, and are expressed in both neurons and SCLC cells.
Peripheral neuropathy is a well known manifestation of ANNA-1 related syndrome, being seen in 60-95% of patients 1,2.Subacute sensory neuronopathy ( SSN) which results from destruction of sensory neuron cell bodies in dorsal root ganglia is the most frequent presentation. However, motor and autonomic neuron cell bodies can also be involved, rarely in isolation, and more commonly in association with SSN. The course of disease is usually subacute or progressive, and rarely acute and resembling GBS 2. EMG commonly shows sensory ganglionopathy (diffusely abnormal or absent SNAPs with normal motor responses and needle EMG), but motor neuropathy and demyelinating features were reported in about one fifth of the patients 2. As Hu antigen is not expressed in the peripheral nerves, peripheral neuropathy could be caused by autoimmunity to other nerve antigens 3. Other features of ANNA-1 related paraneoplastic syndrome include encephalomyelitis (~40% of cases) and autonomic neuropathy (~30%).
References
1. Dalmau J, Graus F, Rosenblum MK, Posner JB. Anti-Hu–associated paraneoplastic encephalomyelitis/sensory neuronopathy. A clinical study of 71 patients. Medicine 1992;71(2):59-72.
2. Camdessanche JP, Antoine JC, Honnorat J, Vial C, Petiot P, Convers P, Michel D. Paraneoplastic peripheral neuropathy associated with anti-Hu antibodies. A clinical and electrophysiological study of 20 patients. Brain : a journal of neurology 2002;125(Pt 1):166-175.
3. Antoine JC, Mosnier JF, Honnorat J, Convers P, Absi L, Lapras J, Michel D. Paraneoplastic demyelinating neuropathy, subacute sensory neuropathy, and anti-Hu antibodies: clinicopathological study of an autopsy case. Muscle & nerve 1998;21(7):850-857.