Autoimmune diseases are caused by aberrant response of immune system directed against triggering epitopes.(1)Coincidental occurrence of multiple autoimmune disorders in given patient suggests either common or similar pathogenetic mechanisms.(1)The concept of molecular mimicry hold that an agent may share epitopic determinants with nervous system tissues and incites immune responses. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Multiple Sclerosis (MS) are acquired diseases evolving with progressions and relapses. Zéphir et al (2)recently reported five patients with relapsing demyelinating disease affecting CNS and PNS and reviewed previously described cases. In Zephir et al (2)patients, demyelinating process started in CNS with subsequent extension to peripheral nerves. We experienced three patients affected by concurrent, both symptomatic, peripheral and central demyelination. Chronology of their histories demonstrated that bouts of symptoms initiated within PNS with extension to CNS. Case 1 when aged 18 years, developed recurrent episodes of unilateral complete facial palsy and distal paresthesias. On 1st admission, deep jerks were unevokable. Brain magnetic resonance imaging (MRI),visual evoked responses (VERs),nerve conduction were normal.Ten years later, patient experienced hand tremor,distal extremity numbness,imbalance.On examination, there were sustained nystagmus on either lateral gaze, limb ataxia, positive Romberg sign, 3/5 MRC scale distal weakness, loss of perception, areflexia. Routine laboratory tests were normal, except for hypothyroidism due to earlier thyroiditis. CSF had no oligoclonal IgG bands (OCIgG).Antibody assay for gangliosides, myelin associated glycoprotein (MAG)was negative.PMP22 point mutations,duplications,deletions and P0,connexin 32 mutations were negative. Brain MRI was normal whereas there were multiple spinal cord enhancing lesions fromC1 to Th7. Electrophysiology showed demyelinating polyneuropathy with proximal and distal motor conduction block (CB.(3)Sural potential had low amplitude(3 uV,normal >6.High doses of methylprednisolone(1gr i.v daily for 3 days) had benefit. Four months later, patient presented with vertigo,dysarthria, blurred vision. VERs were altered. On MRI, a bulbar enhancing lesion was found. Methylprednisolone i.v was repeated.Immune globulin was afterwards administered (1gr /kg/ body weight)every two to three months. During following five years, serial electrophysiology confirmed demyelination as indicated by slowed motor velocity (within 28 and 32 m/sec),delayed F waves,dispersed motor responses throughout. Brain and spinal cord MRI showed dissemination, fulfilling Barkhof's criteria for MS diagnosis.(4)The disease had no further clinical recurrences. Case 2 since early youth experienced tingling pain in hands and feets. Fourteen years later, patient was admitted because of myalgias and limb distal numbness. Neurological examination revealed 3/5 MRC proximal and distal extremity weakness,areflexia. Electrophysiology demonstrated sensorimotor demyelinating neuropathy with CB in both median and ulnar nerves.Muscle biopsy had neurogenic features.Laboratory tests and brain MRI were unremakable.At age of 35, patient was admitted because of blurred vision, imbalance,acral paresthesias. On examination, there were tremor,limb,trunk ataxia, areflexia, distal loss of strength (2/5 MRC),impaired sensation. CSF had increased protein (50 mg/dl, normal < 45) and OCIgG bands.VERs were normal.Brain MRI showed numerous periventricular and subcortical T2 hyperintense lesions, fulfilling Barkhof’s criteria for dissemination.(4) Electrophysiology confirmed ongoing demyelination in peripheral nerves.(3) No antiganglioside nor anti-MAG antibodies were detected. Oral prednisone was given (50 mg every other day).One year later, patient developed renal insufficiency due to hypertension. Cognitive decline and seizures complicated the illness, which was marked by recurrent motor deficits in lower limbs. Our third case,with past history of hyperthyroidism, presented after two years of lumbar pain,distal extremity numbness,waddling gait. On examination, extremity strength was graded 3/5 proximally, 2/5 distally on MRC scale. Moreover,there were stepping gait,areflexia,muscular atrophy,distal impairment of all perception modalities. Electrophysiology revealed sensorimotor demyelinating neuropathy, without CB. Sural biopsy showed endoneural oedema, fiber loss, epineurial T cell infiltrates.VERs, MRI and CSF were unremarkable.Immune globulin (0,4 gr /kg body weight for four days ) was given and repeated with benefit.Type II diabetes was discovered three years later. Patient motor deficits relapsed twice within five years. On latest examination,there were nystagmus, scanned speech, trunk ataxia. Brain MRI showed multiple T2 hyperintense, enhancing white matter lesions suggestive of MS.(4) Serial electrophysiology confirmed peripheral nerve demyelination. Discussion: Our patients presented stepwise recurrent and chronically progressive demyelinating process initiated within PNS with subsequent extension to CNS. PNS presenting symptoms predated by ten years in case 1,by two to three years in case 2 and 3 CNS clinical and neuroradiological changes, which progressed in parallel. Transiently their disease responded to steroids or immunomodulating treatment. None had antecedent infections. Antibodies to gangliosides and MAG were absent. No connexin 32, P0, PMP 22 mutations were found. All patients had associated thyroid disfunction: case 2 developed diabetes. Exact significance of such association,if any, is not clear,though it may suggest susceptibility to multiple immune mediated diseases. Case 2 developed renal failure related to hypertension years after neurologic onset. CIDP of our patients was diagnosed on account of required criteria.(3) Sural biopsy confirmed diagnosis of case 3. VERs were abnormal only in case 2. Interestingly, CSF obtained after onset of peripheral signs showed OCIgG only in second case. MRI abnormalities in all fullfilled Barkhof’s criteria for dissemination.(4) Concurrent CIDP and CNS demyelination may progress either overtly or clinically silent.(2) Myelin P1 expressed in peripheral nerves is identical to central myelin basic protein; moreover cross reactivity between cryptic antigenic targets in CNS and PNS might be crucial.(1-2) Zephyr et al (2) on account of clinical and laboratory data consider their patients affected by new demyelinating entity distinct from classical MS and CIDP:none of their cases had CB or abnormal temporal dispersion although fulfilled criteria for CIDP.(3) None of Zephyr et al patients (2) had CSF OCIgG bands, one had initial pleiocytosis, three hyperproteinorrachia. It is known that MS patients may lack oligoclonal bands.(5) Among the 100 CIDP described by Bouchard et al (5) two out of five with symptomatic CNS involvement had OCIgG bands , three MRI features of MS. Overall neurologic features of reported cases (2,5) raise issue as to whether they represent overlap version or distinct variant of CIDP and MS. Regardless which mechanism may underlie their disease, patients with concurrent CNS and PNS demyelination seem to share rather similar immunopathogenesis suggesting a spectrum of dysimmune attacks against myelin.(1, 2,5 )

References 1. Koller H,Schoeter M, Kieseier BC, Hartung HP . Cronic inflammatory demyelinating polyneuropathy-update on pathogenesis , diagnostic criteria and therapy. Curr Opin Neurol 2005;18: 273-8. 2. Zéphir H, Stojkovic T, Latour P et al Relapsing demyelinating disease affecting both the central and peripheral nervous systems. J Neurol Neurosurg Psychiatry 2008;79:1032-39. 3. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology 1991 ;41: 617-18 4. Barkhof F, Filippi M, Miller DH.Comparaison of MRI imaging criteria at first presentation to predict conversion to clinically definite multiple sclerosis.Brain 1997;120:2059-69. 5. Bouchard C, Lacroix C, Plante’ V et al .Clinicopathologic findings and prognosis of chronic inflammatory demyelinating polyneuropathy.Neurology 1999:52: 498-503.

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We read with interest the recent article published by Scheltens et. al. [1] The article helped us in understanding greater insights about AD dementia. As rightly stated by the authors that one magic bullet will never be found, but different therapeutic agents may benefit different subgroups of patients. The identification and importance of cognitive AD subtypes for making differentiated diagnoses will also help in the further cognitive rehabilitation of AD patients. Out of the three clusters classified by the authors, one was the memory indifferent group wherein all patients were diagnosed with probable AD with a MMSE score with mean 14. The review suggests how an MMSE score is not supportive of AD diagnosis. [2][3] We would like to know the view of the authors on how memory indifferent group a MMSE score. As the neuropsychological test battery used by the institute is dynamic, the use of MMSE in future can be avoided as it is not a sensitive measure for diagnosis of AD. There are other available measures which are found to be more sensitive than MMSE for cognitive screening like MoCA. [4][5]Attention is one of the cognitive domains that are found to be impaired in people suffering from AD. [6] It's intriguing to know from the results of the paper which show how attention is comparatively less affected in these patients. Lastly, we would like to know the age of the patients as the article talks about the younger patients who were six times more likely to be classified in MOD- VISP, three times likely to be classified in SEV-DIFF and two times likely to be classifies in MILD-EXE. The information about the different age ranges would provide a better insight. We would like to thank the authors for carrying out this research as it provides greater understanding of the AD.

1. Scheltens, N. M., Galindo-Garre, F., Pijnenburg, Y. A., van der Vlies, A. E., Smits, L. L., Koene, T., & van der Flier, W. M. (2015). The identification of cognitive subtypes in Alzheimer's disease dementia using latent class analysis. Journal of Neurology, Neurosurgery & Psychiatry, jnnp-2014. 2. Roselli, F., Tartaglione, B., Federico, F., Lepore, V., Defazio, G., & Livrea, P. (2009). Rate of MMSE score change in Alzheimer's disease: influence of education and vascular risk factors. Clinical neurology and neurosurgery, 111(4), 327-330. 3. Galasko, D., Klauber, M. R., Hofstetter, C. R., Salmon, D. P., Lasker, B., & Thal, L. J. (1990). The Mini-Mental State Examination in the early diagnosis of Alzheimer's disease. Archives of Neurology, 47(1), 49- 52. 4. Neufang, S., Akhrif, A., Riedl, V., F?rstl, H., Kurz, A., Zimmer, C., & Wohlschl?ger, A. M. (2011). Disconnection of frontal and parietal areas contributes to impaired attention in very early Alzheimer's disease. Journal of Alzheimer's Disease, 25(2), 309-321. 5. Pendlebury, S. T., Markwick, A., de Jager, C. A., Zamboni, G., Wilcock, G. K., & Rothwell, P. M. (2011). Differences in cognitive profile between TIA, stroke and elderly memory research subjects: a comparison of the MMSE and MoCA. Cerebrovascular diseases (Basel, Switzerland), 34(1), 48-54. 6. Larner, A. J. (2012). Screening utility of the Montreal Cognitive Assessment (MoCA): in place of-or as well as-the MMSE?. International Psychogeriatrics, 24(3), 391. 7. Calderon, J., Perry, R. J., Erzinclioglu, S. W., Berrios, G. E., Dening, T., & Hodges, J. R. (2001). Perception, attention, and working memory are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's disease. Journal of Neurology, Neurosurgery & Psychiatry, 70(2), 157-164.

Conflict of Interest:

None declared

Dear Editor,

I read with interest the article by Viegas et al. 1 about the symptomatic, radiological and pathological involvement of the hypothalamus in neuromyelitis optica (NMO). Their case review of a young lady presented with spontaneous vomiting and behavioral change, confirmed the diagnosis of NMO after the identification of aquaporin 4 antibody(AQP4 Ab).

We also have many patients presented with the similar symptoms which later diagnosed of NMO whether by the identification of AQP4 Ab or according to the revised NMO diagnostic criteria. 2 Some patients presented with prolonged nausea for 1 month, or even combined with confusion, but without significant gastroenterology abnormality. Some resolved later spontaneously without particular treatment, but some need high dose steroid treatment or plasma exchange.

As a neurologist in Asian country, NMO patients are more frequent encountered and are easily being recognized when presenting with optic neuritis or myelitis. However, NMO patients with brainstem involvements as the case reporting are not easily being diagnosed, especially during the first attack. We clinician should be aware of the brainstem symptoms in young ladies who are at risk of NMO.

References

1. Viegas S, Weir A, Esiri M. et al.
Symptomatic, radiological and pathological involvement of the hypothalamus in neuromyelitis optica.
J Neurol Neurosurg Psychiatry 2009;80:679-82

2. Wingerchuk DM, Lennon VA, Pittock SJ, et al.
Revised diagnostic criteria for neuromyelitis optica.
Neurology. 2006;66:1485-9.

No conflict of interest

We would like to draw attention to one important point in regard to hyperammonaemic encephalopathy which was not mentioned in the recent excellent article by Sutter and Kaplan discussing the imaging features of encephalopathy.

The cases of hyperammonaemic encephalopathy with neuroimaging features number less than 10 in the reported literature. As the authors stated they can develop cortical signal abnormalities.

However having recently had experience with three cases of hyperammonaemia we noted despite the very diffuse cortical signal change, the signal change didn't involve the perirolandic cortex, in each of the three cases. This was noted in all but one of the reported cases in the literature.

It is worth drawing attention to this, as this radiological feature may be a feature which is quite specific to hyperammonaemia. Clearly this is observation is based on a very small number of patients, but is worth bearing in mind when assessing patients with cortical signal change, which may spare the perirolandic cortex.

As an explanation for this process, it is possible that this is related to cortical cytoarchitecture (perineuronal nets-abundent in perirolandic cortex [1])/receptor characteristics leading to a differential sensitivity to the toxic insult of elevated ammonia.

Reference:

[1] Karaarslan E, Arslan A. Perirolandic cortex of the normal brain. Low signal intensity on turbo FLAIR MR images. Radiology. 2003;227:538-541

Conflict of Interest:

None declared