Dear Sir, We read with great interest the case report by Dattani and Jackson detailing a case of potential cardioembolic stroke in a young man with sickle cell anemia (SCA), without significant cerebral vasculopathy but with PFO. We have conducted a controlled clinical study to determine the prevalence of potential left-to-right shunting (intracardiac or intrapulmonary) in children with SCA and overt clinical stroke using contrasted echocardiography in 147 children with SCA +overt stroke and a control group of 123 children without SCA or stroke. Right-to-left shunting was defined as any potential shunting detected by any method (conventional 2D, Doppler, or contrasted echocardiogram, with 2 contrast injections without Valsalva and 2 injections with Valsalva). We found that the prevalence of potential right-to-left shunting was significantly higher in the SCA+stroke group than in controls (45.6% vs 23.6%, p< 0.001). In post hoc analyses, the SCA+stroke group had a higher prevalence of intrapulmonary (23.8% vs 5.7% p<0.001) but not intracardiac shunting (21.8% vs 18.7%, p=0.533) (Dowling, et al., 2016).

We agree with the Dattani and Jackson, that adults and children with SCA, while at high risk for stroke from SCA-specific risk factors such as sickle vasculopathy, are also at risk for stroke from the "traditional" risk factors for stroke in adults, including potentially treatable risk factors such as paradoxical embolization across a PFO (Dowling and Ikemba, 2011).

Common SCA related conditions such as acute chest syndrome or pulmonary hypertension, as well as anemia itself, can increase right heart pressures, favoring right-to-left shunting and thus favoring paradoxical embolization. In patients without SCA, hypercoagulable states predispose to paradoxical embolization in adults with potential shunting and SCA is itself a hypercoagulable state. Studies of fat embolization syndrome in SCA also support the role of paradoxical embolization syndrome in SCA. Thus, we concur that both children and adults with SCA and stroke warrant more extensive clinical evaluation for "traditional" risk factors for stroke, particularly as they may be amenable to treatment.

We suspect that similar mechanisms may be involved in the etiology of at least some of the "silent cerebral infarctions" that can be detected by MRI in up to 40% of children with SCA. We concur that further research is needed in this area but applaud the authors for highlighting the need for exploration of alternative etiologies for stroke in patients with SCA, and raising the clinical awareness of other potentially treatable stroke etiologies in this high risk population.

Michael Morgan Dowling, MD, PhD, MSCS Departments of Pediatrics and Neurology & Neurotherapeutics University of Texas Southwestern Medical Center, Dallas, Texas

Fenella J Kirkham, MD, FRCP, FRCPCH Developmental Neurosciences UCL Institute of Child Health London, UK

References

Dattani A, Jackson A, The cause of the stroke: a diagnostic uncertainty. BMJ Case Rep. 2017 doi:10.1136/bcr-2016-218358.

Dowling, M.M. & Ikemba, C.M. (2011) Intracardiac shunting and stroke in children: a systematic review. Journal of Child Neurology, 26, 72-82.

Dowling MM, Quinn CT, Ramaciotti C, Kanter J, Osunkwo I, Inusa B, Iyer R, Kwiatkowski JL, Johnson C, Rhodes M, Owen W, Strouse JJ, Panepinto JA, Neumayr L, Sarnaik S, Plumb PA, Dlamini N, Kirkham F, Hynan LS; PFAST Investigators. Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke. Br J Haematol 2017 Jan;176(2):300-308

Disclosures The authors were supported by the Doris Duke Charitable Foundation. They have no other disclosures and no conflicts of interest to report.

Conflict of Interest:

None declared

Dear Editor,

We read with interest the case report concerning a transient global amnesia (TGA) in an individual who was previously submitted to a session of whole body cryotherapy (WBC).1

The scientific literature is already sufficiently wide to realize that the WBC is a safe procedure, while it could seem apparently dangerous due to very low temperature of the air used in the chambers during treatment.2 Only burns owing to sweat or water traces are reported as adverse events, considering some pathological, universally accepted, conditions as exclusion criteria for the treatment.3-9

It is possible that some rare adverse events are neither known nor described in literature, thus possible pathological modifications of metabolism or behaviour can be important. However, in the case report,1 in order to build on a robust hypothesis about WBC-induced TGA, we believe that additional findings are needed. The patient previously underwent to WBC, thus the direct cause-effect relationship is in doubt; we outline that a standard treatment is based on two or three weeks (10-15 sessions). Moreover, the type of treatment should be more deeply detailed: was that a classical cryochamber doing a whole-body treatment or, instead, a cryosauna which is used to treat the body but the head; in the latter case the nitrogen could partially escape possibly causing nervous symptoms.

The anamnestic evaluation lacks of drugs eventually taken by the individual and of mental reactivity and cognition evaluation, in order to exclude early sign of cognitive impairment due to Alzheimer or similar diseases. Furthermore, since the speculative association between WBC and TGA, it should be also taken into account the possible side effects (i.e., amnesia) of the proton pump inhibitors (PPI, e.g., omeprazole), taken by the patient, which were previously reported by Fireman et al.10 More recently, Feng et al. also reported about the psychotic symptoms of dissociative disorder, including amnesia, in a patient treated with clarithromycin and the PPI rabeprazole.11 Hence, if cold could be a risk factor for TGA, as reported by the authors,1 also the PPI use cannot be excluded as a potential trigger.

The description of the case is important to outline the impact of WBC on nervous system, since this procedure is now indicated for the symptomatic treatment of nervous and psychiatric disorders, after the successful symptomatic treatment of chronic inflammatory ones.12,13 However, care should be taken in associating this universally considered safe procedure with possibly spurious, and not surely associated, adverse events.

References

1. Carrad J, Lambert AC, Genn? D. Transient global amnesia following a whole-body cryotherapy session. BMJ Case Rep. Epub Aehad of Print. doi: 10.1136/bcr-2017-221431

2. Lombardi G, Ziemann E, Banfi G. Whole-Body Cryotherapy in Athletes: From Therapy to Stimulation. An Updated Review of the Literature. Front Physiol 2017;8:258. doi:10.3389/fphys.2017.00258

3. Cholewka A, Stanek A, Sieron A, Drzazga Z. Thermography study of skin response due to whole-body cryotherapy. Skin Res Technol 2012;18(2):180-7. doi:10.1111/j.1600-0846.2011.00550.x

4. Hausswirth C, Schaal K, Le Meur Y, et al. Parasympathetic activity and blood catecholamine responses following a single partial-body cryostimulation and a whole-body cryostimulation. PloS One 2013;8(8):e72658. doi:10.1371/journal.pone.0072658

5. Demoulin C, Vanderthommen M. Cryotherapy in rheumatic diseases. Joint Bone Spine 2012;79(2):117-8. doi:10.1016/j.jbspin.2011.09.016

6. Louis J, Schaal K, Bieuzen F, et al. Head Exposure to Cold during Whole-Body Cryostimulation: Influence on Thermal Response and Autonomic Modulation. PloS One 2015;10(4):e0124776. doi:10.1371/journal.pone.0124776

7. Pournot H, Bieuzen F, Louis J, et al. Time-course of changes in inflammatory response after whole-body cryotherapy multi exposures following severe exercise. PloS One 2011;6(7):e22748. doi:10.1371/journal.pone.0022748

8. Kruger M, de Marees M, Dittmar KH, et al. Whole-body cryotherapy's enhancement of acute recovery of running performance in well-trained athletes. Int J Sport Physiol Perform 2015;10(5):605-12. doi:10.1123/ijspp.2014-0392

9. Schaal K, Le Meur Y, Louis J, et al. Whole-Body Cryostimulation Limits Overreaching in Elite Synchronized Swimmers. Med Sci Sports Exerc 2015;47(7):1416-25. doi:10.1249/MSS.0000000000000546

10. Fireman Z, Kopelman Y, Sternberg A. Central nervous system side effects after proton pump inhibitor treatment. J Clin Gastroenterol 1997;25(4):718.

11. Feng Z, Huang J, Xu Y, et al. Dissociative disorder induced by clarithromycin combined with rabeprazole in a patient with gastritis. J Int Med Res 2013;41(1):239-43. doi: 10.1177/0300060513475384.

12. Bettoni L, Bonomi FG, Zani V, et al. Effects of 15 consecutive cryotherapy sessions on the clinical output of fibromyalgic patients. Clin Rheumatol 2013;32(9):1337-45. doi: 10.1007/s10067-013-2280-9.

13. Bouzigon R, Grappe F, Ravier G, Dugue B. Whole- and partial-body cryostimulation/cryotherapy: Current technologies and practical applications. J Therm Biol. 2016;61:67-81. doi: 10.1016/j.jtherbio.2016.08.009.

Conflict of Interest:

None declared

Sir, Its with interest that I read the small and crisp description and medical images related to Artery of Percheron infarct.

The diagnosis of this condition indeed is sometimes difficult and requires clinical suspicion accompanied by proper radiological imaging.

What i would also like to highlight is the fact that its not only the imaging modality i.e MRI which is required,or the sequence DWI/ADC which is also important, the imaging machinery should also be optimal i.e a magnetic strength of at least 1.5 tesla or higher.

I emphasize this point because many MRI machines in the Indian context are suboptimally designed to pick up these important but often small lesions and prescribing physicians often donot have the proper knowledge and thus fail to arrive at a proper diagnosis.

Thanks and regards,

Dr Deep Das Consultant Interventional Neurology Kolkata, West Bengal, India

Conflict of Interest:

None declared

Dear Editor,

We read with interest the work by Haywood et al.[1] dealing with the treatment of a 67 years old Caucasian woman with a 4-day history of sore throat, dysphagia, fever and nasal blockage. During the examination it was revealed a swollen neck and pharyngeal pseudomembranes, positive on culture for Corynebacterium ulcerans after a throat swab, with toxin expression confirmed on PCR and Elek testing. The patient was diagnosed of classical respiratory diphtheria, and the diagnosis was later confirmed on the patient's domesticated dog, which was thought to be the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery.

Zoonotic infections are defined, in general, as infections transmitted from animal to man (and, less frequently, vice versa), either directly (through direct contact or contact with animal products) or indirectly (through an intermediate vector, such as an arthropod)[2]. Zoonotic disease may affect ENT districts. Unfortunately, literature is often limited to single case reports from different countries and does not allow adequate appreciation of the problem.

Otorhinolaryngologists often lack in-depth knowledge of zoonotic diseases, which complicates etiological identification and treatment and control strategies.

In our study we already considered, examining a total of 164 articles, that larynx was the most commonly involved ENT organ. Otherwise, bacteria were the most representative microorganisms involved[2]. As read on another study examined by us, a Corynebacterium ulcerans infection can be responsible for a more aggressive involvement of the ENT district, being capable of involving the total upper airway[3], with the subsequent need to ensure a proper nutrition via a percutaneous endoscopic gastrostomy feeding, as Haywood at al. did facing their case[1].

Another interesting thing to point out is that the ENT manifestations in most of the zoonoses are often produced in immunosuppressed patients, being responsible of disseminated forms which can lead to death rapidly if misdiagnosed[1]. Albeit this, We want to point out, thanks to the work of Vlachogianni et al., a case in which a zoonotic infection caused by Mycobacterium avium was diagnosed in an immunocompetent 78 years-old woman. She presented with a 6-month reddish, oedematous and painless lesion with fine scaling in the right ear. Histology showed numerous granulomas, composed of epithelioid histio-cytes without central necrosis. Cultures grew Mycobacterium avium. An unusual accidental ear injury was the portal of microbial entry. The patient's lesion fully regressed after a 9-month course of antibiotics[4].

This two cases brought to Our attention the fact that the kind of diseases are still of difficult diagnosis for most of the ENT specialists, and need to be more pointed out by the Scientific Community, paying particular attention during the anamnesis.

1. Haywood MJ, Vijendren A, Acharya V, Mulla R, Panesar MJ. Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding. BMJ Case Rep. 2017 Mar 6;2017. pii: bcr2016218408. doi: 10.1136/bcr-2016-218408.

2. Galletti B, Mannella VK, Santoro R, Rodriguez-Morales AJ, Freni F, Galletti C, Galletti F, Cascio A. Ear, nose and throat (ENT) involvement in zoonotic diseases: a systematic review. J Infect Dev Ctries. 2014 Jan 15;8(1):17-23. doi: 10.3855/jidc.4206.

3. Aaron L, Heurtebise F, Bachelier MN, Guimard Y. Pseudomembranous diphtheria caused by Corynebacterium ulcerans. Rev Med Interne. 2006 Apr;27(4):333-5. Epub 2006 Jan 6.

4. Vlachogianni P, Volosyraki M, Stefanidou M, Krueger-Krasagakis S, Evangelou G, Haniotis V, Kofteridis D, Maraki S, Krasagakis K. Mycobacterium avium Auricular Infection in an Apparent Immunocompetent Patient: A Case Report. Folia Med (Plovdiv). 2016 Apr-Jun;58(2):131-5. doi: 10.1515/folmed-2016-0012.

Conflict of Interest:

None declared