Dear Editor,

Dr Hintzen and Dr van den Born describe a patient with acute zonal occult outer retinopathy (AZOOR) who also fulfilled the criteria of clinically definite multiple sclerosis. AZOOR is a rare, newly recognized retinal disorder occurring predominantly in young Caucasian females. [1] The aetiology remains unknown, but an inflammatory origin is suspected. [1][2] As reported by Gass et al. [1], the inflammatory signs typically develop within several weeks following the onset of AZOOR, and probably result from an inflammatory response to the dead retinal receptor cells. Occasionally, weeks or months later, narrowing of the retinal vessels, particularly the retinal arteries, perivascular sheathing and reactive changes in the RPE occur, including hypopigmentation and migration of RPE into the overlying retina similar to that occurring in RP in the zones of receptor cell loss. Given this background, in our opinion, while on the one hand, the authors fulfilled the criteria of clinically definite multiple sclerosis, on the other hand the ophthalmic examination didn’t fulfil the clinical criteria of AZOOR. In fact, given that funduscopy showed areas with depigmentation of retinal pigment epithelium and scattered intraretinal pigmentation (bone spicule pigmentation), narrowed retinal vessels and a pale optic nerve in both eyes, the patient could be either diagnosed with retinitis pigmentosa, associated with multiple sclerosis, either with late AZOOR. In addition, visual field analysis of the right eye revealed a concentric scotoma, typical of retinitis pigmentosa (RP); the field of the left eye was severely constricted, typical, again, of RP. AZOOR is currently a diagnosis made entirely on clinical grounds and is frequently a diagnosis of exclusion. Given that several reports [3–5] have appeared to confirm Gass’s initial suspicion that there is considerable coincidence between AZOOR and the so called ‘‘white dot’’ syndromes, such as MEWDS (multiple evanescent white dots syndrome) and AIBSE (acute idiopathic blind spot enlargement syndrome), we believe that one should look for the inflammatory signs typical of these diseases, in case of suspected early AZOOR. Here we report the case of a 30-year-old women who was diagnosed with early AZOOR, following a complete ophthalmological examination including visual field analysis, electroretinography, fluorescein angiography, indocyanine green angiography. This young women also fulfilled the criteria of clinically definite multiple sclerosis. Showing some clinical features of early AZOOR associated with multiple sclerosis from our patient (figure), we want to highlights the need for an early correct approach of such cases. Given that AZOOR is frequently a diagnosis of exclusion, we believe that only following an early complete ophthalmological and neurological examination showing the early inflammatory signs one should make the definitive diagnosis of AZOOR associated with multiple sclerosis.

Giuseppe Querques

Department of ophthalmology, University of Foggia

Figure 1

Colour fundus photography showing some inflammatory signs such as little white dots and mild optic disk edema (top left panel, A). Indocyanine green angiography late frame showing late hypofluorescent lesions scattered at the posterior pole and in mid periphery (bottom left panel, B). MRI frame showing white matter abnormalities (right panel, C).

References

1. Gass JD, Agarwal A, Scott IU. Acute zonal occult outer retinopathy: A long-term Follow-up Study. Am J Ophthalmol 2002;134:329-339.

2. Jampol LM, Becker KG. White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of the autoimmune/inflammatory disease. Am J Ophthalmol 2003;135:376-379.

3. Jacobson S, Morales D, Sun X, et al. Pattern of retinal dysfunction in acute zonal occult outer retinopathy. Ophthalmology 1995;102:1187–96.

4. Volpe N, Rizzo J, Lessell S. Acute idiopathic blind spot enlargement syndrome. Arch Ophthalmol 2001;119:59–63.

5. Holz F, Kim R, Schwartz S, et al. Acute zonal occult outer retinopathy (AZOOR) associated with multifocal choroidopathy. Eye 1994;8:77–83.

Dear Editor,

I have read all the three articles (1), (2), (3), published in Vol .77, 2006, and found them to be very good studies. It also gives a new nsight to Parkinson’s disease and seems to be very useful in our day to day practice. In this connection I would like to add a few things.

Camptocormia was first described by Brodie, in 1918. Reichel G et al, (4) proposed for new classification for camptocormia , as -(a)Primary form, which is a segmental dystonia of abdominal muscles, (b) Secondary forms, where Parkinson’s disease is one of the causes.

Azher S.N. et al ,( 5) also proposed camptocormia to be a heterogeneous disorder having multiple etiologies and needs etiological classification,which also responds poorly to levodopa therapy. D Jaldetti R et al, (6) considered camptocormia to be either a rare form of dystonia or an extreme form of rigidity. In his study the response to levodopa was variable, even in some cases camptocormia was aggravated. Slawek J et al, (7) concluded in his study that camptocormia is probably not a form of dystonia of trunk, but may be dysfunction in other non dopaminergic nigrostrital projection. Since then many theories have been suggested, but the exact pathogenesis of this is not yet clear. F Blotch, et al (1) have tried to link the hypothesis of focal dystonia as primary cause,and focal myopathy as a secondary event. It seems more or less justifiable. Now if dystonia is the primary cause in camptocormia then it is worth trying botulinum toxin as a form of treatment for these camptocormia, but the exact dose, the muscles to be injected needs further studies. Melamed et al, (8) reported that occasional patients may benefit from intramuscular botulinum toxin injection or from deep brain stimulation. However it needs further studies to explore the real pathogenetic mechanism of camptocormia in Parkinson’s disease so as to find the correct mode of treatment.

Micheli F et al, (9) in a patient of camptocormia with Parkinson’s disease reported that camptocormia improved with bilateral pallidal stimulation. Yamada K et al, (10) reported a striking alleviation of camptocormia after chronic bilateral sub-thalamic stimulation, Boulos Paul Bijjenni et al, (11), also reported that bilateral timulation of sub thalamus improves the axial symptoms of Parkinson’s disease. There is also a synergistic effect obtained when levodopa was used in conjunction with bilateral stimulation of sub thalamic nucleus stimulation. So a comparative trial is needed to find out the best form of therapy.

Keeping these in view, patients presenting with camptocormia, should be thoroughly investigated for the presence of Parkinson’s disease. If they are found to have Parkinsons disease, then which modes of treatment is the best for the patient on an individual basis, is the question. Whether the combination of deep brain stimulation of sub-thalamic nucleus and levodpa therapy, or only deep brain stimulation, or levodopa in conjunction with botulinum toxin injection is better, for alleviating the axial dystonia as well as other features of Parkinson’s disease needs a controlled trial.

References

1. F Blotch, J L Houteo, S Tenzenas du Montcel, F Bonneville, F Etchepare, M L Weter, S Rivaud-Pechoux, V Hahn Barma, T Maisonobe, C Behar, J Y Lazennec, E KURYS, I Arnuf, A M Bonnet, Y Agid. Parkinson’s disease with camptocormia. J Neurol Neurosurg Pschiatry, 2006,77,1223-1228

2. A-C Lepoutre, D Devos, A Blanchard, Dauphin, V Pardessus, C A Maurage, D Ferriby, J F Hurtevent, A Cotton, A destee, L Defebvre. A specific patteren of camptocormia in Parkinson’s Disease. J Neurol Neurosurg Psychiatric,2006,77,1229-1234.

3. R Djaldetti,E Melamed. Camptocormia in Parkinson’s disease: new insights. J Neurol Neurosurg Pschiatry, 2006, 77, 1205.

4. Reichel G, Kirchhofer U, Stenner A. Camptocormia-segmental dystonia. Proposal of a new defination for an old disease. Nervenarzt 2001,April,72,(4):281-285. Abstract.

5. Azher S N,Jancovic J. Camptocormia: pathogenesis, classification, and response to therapy. Neurology, 2005, Aug 9,65,(3):355-359.

6. Djaldetti R, Mosberg-Galili R,Soroka H, Merims D, Melamed E. Camptocormia(bent spine) in patients with Parkinson’s disease-charecterization and possible pathogenesis of an unusual phenomena. Mov Disord, 1999, May, 14(3):443-447.

7. Slawek J, Derejko M, Camptocormia,a rare form of motor system disorders in Parkinson’s disease. Neurol Neurochir Pol. 2001 35(6): 1133-40 Abstract.

8. Melamed E, Djaldetti R. Cam,ptocormia in Parkinson’s disease. J Neurol.Dec,253 Suppl7,vii14-vii16.

9 .Micheli F, Cersosimo M G, Piedimonte F. Camptocormia in a patient with Parkinson’s disease: beneficial effects of pallidal deep brain stimulation. Case report, JNeurosurg.2005, Dec, 103, 6):1081-1083.

10. Yamada K, Goto S, Matsuzaki K, TamuraT, MuraseN, ShimazuH, Nagahiro S,Kuratsu J,Kaji R. Alleviation of camptocormia by bilateral subthalamic nucleus stimulation in a patient with Parkinson’s disease. Parkinsonism Relat Disorder 2006, 12,(6):372-5,Epub2006 May 30.Abstract.

11. Boulos-Paul Bejjani,David Gervais,Isbelle Arnulf Savas Papadopoulos,Sophie Demeret,Anne Marie Bonnet,Philippe Cornu,PhilippeDamier,Yves Agid. Axial Parkinsonian symptoma can be improved:the role of levodopa and bilateral subthalmic stimulation. J Neurol Neurosurg Psychiatric, 2000, 68,595-600.

Dear Editor,

Transient global amnesia (TGA) is a clinical syndrome characterized by a sudden onset of anterograde and retrograde amnesia in the absence of other neurological signs and symptoms, which is resolved within 24 hours. Although the etiology of TGA remains unknown, recently Lewis 1) suggested that a Valsalva-like action appears to be a common triggering event among patients with TGA. Although TGA following medical procedures has not been established, Hiraga and Matsunaga 2) reported encountering three patients who developed TGA after upper gastrointestinal endoscopy (UGI). However, they did not perform single photon emission CT (SPECT). We dealt with a case of TGA occurring immediately after UGI and performed SPECT test during the TGA attack.

Case report. A middle aged right-handed patient underwent UGI by a veteran endoscopist. The UGI was administered under lidocaine spray anesthesia without further premedication. There was no history of migraine, epilepsy, or cerebrovascular disease. When the endoscope was being removed, the patient held their breath and strained as in the Valsalva maneuver, but no cardiac arrhythmia was noted during electrocardiographic monitoring. Just after the examination, the patient suddenly developed complete anterograde amnesia and retorograde amnesia of the recent past five or six years. Neurological examination results were normal except for severe memory impairment. Magnetic resonance imaging (MRI) of the brain, including diffusion-weighed imaging (DWI) of the brain performed during the attack, three hours after onset, showed no abnormalities. Cervical artery color duplex sonography and electroencephalography (EEG) findings were normal during the attack. The first Tc- 99m ECD SPECT study was performed during the attack, four hours after onset, and showed hyperperfusion in the right thalamus.

Figure 1a-b(A) First SPECT study during the transient global amnesia (TGA) attack discloses a focus of increased activity uptake in the right thalamus (arrow). (B) Second SPECT study one month after TGA discloses decreased activity uptake in the same region as that of the previously demonstrated increased uptake.

Both hematological and hemocoagulation screening test results were normal. Twelve hours after onset, the patient had recovered completely but a memory gap for a part of the previous day remained. In the second SPECT study, conducted 1 month later, no asymmetry was detected either visually or through quantification. Findings for the second brain MRI, also conducted 1 month later, were normal, too.

Discussion.

Our patient met all the proposed criteria for TGA. The amnesia of our patient was not produced by anesthesia, because the patient did not receive any sedation or premedication except for lidocaine spray. Furthermore DWI MRI of our patient did not show hyperintensity, thus making an ischemic origin unlikely. Although the occurrence of TGA after UGI is rare, two other reports of TGA following UGI 3-4) have been published, and both cases were from Japan as in the study by Hiraga and Matsunaga 2). These cases did not receive any sedation, because UGI is usually administered without sedation in Japan. TGA may be overlooked in some cases in Western countries because the transient nature of the event and concomitant sedation may obscure TGA occurrence. Hiraga and Matsunaga 2) proposed that autonomic dysfunction or emotional stress might be a possible cause of TGA. In addition, Valsalva-like action without sedation may also have been a triggering factor in our case as suggested by Lewis.

While none of the previously reported cases were examined by SPECT after UGI, our SPECT findings support the notion that TGA can occur after UGI. SPECT performed during TGA of our patient showed increased activity uptake in the right thalamus. Spontaneous temporal lobe seizures are unlikely to have occurred because EEG during the episode was normal and no epileptic seizures were observed.�@Although SPECT findings have shown hypoperfusion in memory relevant brain structures in almost all patients with TGA, some studies reported transient hyperperfusion in the left medial temporal lobe during TGA attack 5).

Although TGA is a rare complication of medical procedures, physicians should be aware of its potential occurence.

References

1. Lewis SL. Aetiology of transient global amnesia. Lancet 1998;352:397-99.

2. Hiraga A, Matsunaga T. Trasient global amnesia after gastroscopy. J Neurol Neurosurg Psychiatry 2006;77:995-996.

3. Joshita Y, Mineo E, Kihira K, Sato K, Kasano T, Yoshida Y, Ido K, Kimura K, Yoshida M. Rare hazard of gastrointestinal endoscopy. A case of transient global amnesia. Gastroenterol. Endosc 1990;32:589-92. (in Japanese)

4. Sawada Y, Kamihira M, Hirakawa R, Yoshida Y, Imawari M. A case of transient global amnesia precipitated by gastrointestinal endoscopy. Progress of Digestive endoscopy 2002;60:44-46. (in Japanese)

5. Matsuda H, Higashi S, Tsuji S, Sumiya H, Miyauchi T, Hisada K, Yamashita J. High resolution Tc-99m HMPAO SPECT in a patient with transient global amnesia. Clin Nucl Med 1993;18: 46-49.

Dear editor

In response to our article, Spengos et al. suggested that we should evaluate the circadian variation of stroke onset separately for the aetiologically different subtypes of ischaemic stroke. Stroke diagnostic criteria of the registry in our study are based essentially on MONICA manual version 1.1, which classifies cerebral infarction (CIF) into that due to cerebral thrombosis (TMB), embolic brain infarction (EMB) and other or unknown aetiology.[1][2] Unfortunately, it was impossible to separate lacunar stroke (LACS) and atherosclerotic stroke, and both were categorised as TMB in the registry.

The registry categorises CIF into TMB, which accounted for 47.3% of CIF cases (3,582/7,575), EMB which accounted for 15.6% (1,181/7,575) and other or unknown aetiology, which accounted for 37.1% (2,812/7,575).

The percentages of cases of CIF in which stroke onset occurred while the patient was asleep were 16.5%, 13.5% and 11.7%, respectively. The percentage of cases occurring while sleeping was lower among patients with EMB than among those with TMB (P<0.05). The percentages of cases occurring during sleep in both TMB and EMB were greater than those of intracerebral haemorrhage (ICH) and subarachnoidal haemorrhage (SAH) (P<0.005 and <0.001, respectively). The time-specific onset for twelve 2-h periods for separated CIF categories were calculated in the same way as in our article.[2] The cases in which TMB occurred during sleep showed a higher single peak than other categorised CIF during the period from 06:00 to 07:59.

The cases in which EMB occurred during sleep showed a single but lower peak than that of TMB.

Cases of other or unknown aetiology showed a single peak, which was higher than that of EMB but lower than that of TMB.

The cases of TMB, EMB and other in which onset occurred in the waking state showed two similar peaks; a higher peak in the morning and a lower peak in the afternoon. TMB, which accounted for 47.3% of cases of CIF, showed a marked influence on circadian rhythm of whole CIF onset. Spengos et al. reported that onset of LACS was associated with stroke during sleep (SDS).[3] LACS may have accounted for the high percentage of TMB in our study, and influenced circadian variation of onset of the whole CIF, especially onset during sleep or status in sleep.

Spengos et al. expressed doubt about the relation between stroke onset of CIF and variation in blood pressure (BP) according to lack of information of BP on admission. Our study not only suggested that BP dropped during sleep, but also that various changes during sleep, such as the drop in BP, respiratory disorders during sleep and haemostatic functions, are risk factors and triggers for onset of CIF.[2]

The results of our study suggested that sleep or status in sleep was a risk factor for CIF but not for ICH or SAH, because all cases of stroke onset during sleep and with unknown situation occurred equally between midnight and 06:00, and circadian rhythm lost its nadir during the night in CIF, but not in ICH or SAH.[2] Spengos et al. also expressed doubt about our assumption of an equal distribution of SDS between midnight and 06:00. The purpose of this method, which was intentionally biased for circadian variation in all onset situations from midnight to early morning, was not to evaluate circadian variation, but to evaluate the relation between sleep or status in sleep and the risk of occurrence of stroke in each subtype. In the registry, SDS of CIF in which onset time was registered between midnight and early morning accounted for most cases, and the number of SDS cases of CIF in the other time zone was markedly lower. Many of the cases of SDS in which onset occurred during the daytime or was unspecified were supposed to be unconscious and to have been found to have had a stroke late as the patients lived alone or due to the absence of housemates. However, these cases were also exposed to a risk of SDS. We feel that it is appropriate to redistribute SDS during sleeping hours for evaluation of the risk of SDS in our study.

In their recent study, Spengos et al. suggested that there is a relation between bimodal variation of stroke onset and siesta.[3] Bimodal variation of stroke onset has been reported in the UK and Japan, both countries in which siesta is uncommon.[2][4] Therefore, factors other than siesta may be involved. We supposed that BP variation, which showed bimodal variation, is responsible for the bimodal circadian rhythm.[2][5] In our study, we showed that the evening peak from 18:00 to 19:59 is higher than the morning peak of 08:00 to 09:59 among patients with ICH and SAH in which stroke onset occurred during waking hours, whereas CIF showed a higher morning peak.[2] In addition, the reasons for these differences in peak height between ischaemic and hemorrhagic stroke were discussed with regard to haemostatic functions. The reader�fs suggestion that we did not underline these results is mistaken.

As noted by Spengos et al., it is very important to evaluate circadian variation of CIF onset and risk factors and triggers by subtype for aetiological differences. Such studies will provide important information regarding risk factors and triggers of stroke onset.

References

1. World Health Organization MONICA Project. Event Registration Data Component, MONICA Manual Version 1.1. Document for meeting of MONICA Principal Investigators, 1986.

2. Omama S, Yoshida Y,Ogawa A, et al. Differences in circadian variation of cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage by situation at onset. J Neurol Neurosurg Psychiatry published 17 August 2006, 10.1136/jnnp.2006.090373

3. Spengos K, Vemmos K, Tsivgoulis G, et al. Two-peak circadian distribution of stroke onset in Greek patients. A hospital based study. Cerebrovasc Dis 2003; 15: 70-77.

4. Wroe SJ, Sandercock P, Bamford J, et al. Diurnal variation in incidence of stroke: Oxfordshire community stroke project. BMJ 1992;18:155-157.

5. Stergiou GS, Vermmos KN, Pliarchopoulou KM, et al. Parallel morning and evening surge in stroke onset, blood pressure, and physical activity. Stroke 2002;33:1480-1486.