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• Re:Pyramidal tract involvement in HMSN-P?
  Ryuji Kaji
  Published on: 13 April 2016
• Pyramidal tract involvement in HMSN-P?
  Kengo Maeda
  Published on: 13 April 2016

• Published on: 13 April 2016

  Re:Pyramidal tract involvement in HMSN-P?

  • Ryuji Kaji

  We thank Dr. Kengo Maeda for his comments regarding our case report of a patient with Kansai-type proximal-dominant hereditary motor and sensory neuropathy (HMSN-P).[1] He argues that upper motor neuron (UMN) involvement has not been established in HMSN-P because of the following reasons: UMN signs were absent in his 15 patients with Brazilian and Kansai-type HMSN-P; previous studies did not suggest UMN involvement in H...

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  We thank Dr. Kengo Maeda for his comments regarding our case report of a patient with Kansai-type proximal-dominant hereditary motor and sensory neuropathy (HMSN-P).[1] He argues that upper motor neuron (UMN) involvement has not been established in HMSN-P because of the following reasons: UMN signs were absent in his 15 patients with Brazilian and Kansai-type HMSN-P; previous studies did not suggest UMN involvement in HMSN-P; and bilateral Babinski sign and corticospinal tract degeneration in our case might be explained by multiple cerebral infarction. We agree with Dr. Maeda in that UMN involvement has to be carefully assessed in HMSN-P patients. However, we do not exclude the potential UMN involvement in this disease. Detailed examination of the distribution of infarction revealed that it could not explain the diffuse symmetrical involvement of the corticospinal tract seen in our case. Furthermore, another case with Kansai-type HMSN-P had a positive Babinski sign despite the lack of focal lesions in brain magnetic resonance imaging. Abnormal protein aggregation, even if not in UMNs, is also important for the understanding of the pathogenesis of this disease. Although we reported that TAR DNA-binding protein 43 kDa (TDP-43)-positive inclusions were not seen in our case, further investigation under different staining conditions has revealed TDP -43-positive inclusions in neurons of the brainstem nuclei, the anterior horn of the spinal cord, Clarke's nucleus, and the dorsal root ganglia, suggesting another link between HMSN-P and amyotrophic lateral sclerosis (ALS). Clinically, early presentations with prominent fasciculations in proximal muscles without sensory involvement in our series most commonly lead to the diagnosis of ALS by neurologists, although the progression is gradual. Together, we believe that the understanding of HMSN-P in the context of ALS spectrum should contribute to the elucidation of the pathomechanism of the disease.

  References 1. Fujita K, Yoshida M, Sako W, et al. Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry 2011;82:1402-1403.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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• Published on: 13 April 2016

  Pyramidal tract involvement in HMSN-P?

  • Kengo Maeda, neurologist

  Pyramidal tract involvement in HMSN-P?

  Kengo Maeda, Department of Neurology, National Hospital Organization Shiga Hospital 255 Gochi, Higashi-oumi, Shiga 527-8505, Japan Tel: +81-748-22-3030 Fax: +81-748-23-3383 E-mail: maeda-kengo@shiga-hosp.jp

  Dear Editor,

  I have read a postscript 'Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary mo...

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  Pyramidal tract involvement in HMSN-P?

  Kengo Maeda, Department of Neurology, National Hospital Organization Shiga Hospital 255 Gochi, Higashi-oumi, Shiga 527-8505, Japan Tel: +81-748-22-3030 Fax: +81-748-23-3383 E-mail: maeda-kengo@shiga-hosp.jp

  Dear Editor,

  I have read a postscript 'Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy' (HMSN-P)1 by Fujita et al with a great interest. HMSN-P is very rare and is found in only limited area (Two areas in Japan and Brazil). They discovered optineurin-positive inclusions as well as lower motor neuron involvement in the brainstem and spinal cord. They proposed a new classification of HMSN-P into the subgroup of amyotrophic lateral sclerosis (ALS). Also, they described the pathological changes in the lateral columns with neuronal loss in the precentral gyrus. This finding might also have encouraged them to consider the new classification. After I reported three Brazilian brothers with HMSN-P who had Okinawan ancestry2, I went to Brazil to see their siblings and another HMSN-P family3 and saw nine Brazilian HMSN-P patients in all. Moreover, I have seen six HMSN-P of Kansai (Shiga)-type in my hospital (V:3, V:11, V:16, and V:17 of pedigree 1, IV:8 and V:4 of pedigree 2)4. But, none of them showed clear pyramidal tract sign. A report of Shiga-type HMSN-P written in Japanese did not mention the involvement of pyramidal tract5. There was no description of the involvement of the corticospinal tract in the original paper by Takashima et al6. When the lower motor neurons and large sensory neurons in the dorsal root ganglion are severely damaged, pyramidal tract signs might be masked. That might be why we did not find any pyramidal tract signs in HMSN-P patients. I think that involvement of the pyramidal tract in HMSN-P is much more important than the presence of optineurin-positive inclusions in the lower motor neurons. But, we should be careful, because their postscript1 is a single case report. Moreover, the patient had multiple cerebral infarctions. These infarctions might explain the bilateral Babinski sign and pathological changes in the lateral columns. They did not show the density of Bets cells of the precentral gyrus or changes of the myelinated fibres in the posterior limbs of the internal capsule. Although their pathological study is quite important in the understanding of the pathomechanisms of HMSN-P or familial ALS, I think that it might be too early to propose the new classification of HMSN-P into the subgroup of ALS.

  References 1)Fujita K, Yoshida M, Sako W, et al. Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry 2011;82:1402-3. 2)Maeda K, Sugiura M, Kato H, et al. Hereditary motor and sensory neuropathy (proximal dominant form, HMSN-P) among Brazilians of Japanese ancestry. Clin Neurol Neurosurg 2007;109:830-2. 3)Patroclo CB, Lino AMM, Marchiori PE, et al. Autosomal dominant HMSN with proximal involvement: New Brazilian cases. Arq Neuropsiquatr 2009;67:892- 6. 4)Maeda K, Kaji R, Yasuno K, et al. Refinement of a locus for autosomal dominant hereditary motor and sensory neuropathy with proximal dominancy (HMSN-P) and genetic heterogeneity. J Hum Genet 2007;52:907-14. 5)Takahashi M, Mitsui Y, Yorifuji S, et al. Clinical report of hereditary motor and sensory neuropathy with proximal dominance in Shiga prefecture. Rinsho Shikeigaku 2007;47:571-6. 6)Takashima H, Nakagawa M, Nakahara K, et al. A new type of hereditary motor and sensory neuropathy linked to chromosome 3. Ann Neurol 1997;41:771-80.

  Conflict of Interest:

  None declared

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  Conflict of Interest:
  None declared.

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