Perioperative management of a CADASIL type arteriopathy patient

J. H. Dieu* and F. Veyckemans

Service d’Anesthésiologie, Cliniques universitaires Saint-Luc, Catholic University of Louvain Medical School, Avenue Hippocrate, 10-1821, B-1200 Brussels, Belgium

Corresponding author: E-mail: jhdieu@hotmail.com

Accepted for publication: April 10, 2003


    Abstract
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 Abstract
 Introduction
 Case description
 Discussion
 References
 
We report the anaesthetic management of a patient suffering from an ischaemic arteriopathy of the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) type. The anaesthetic implications of this pathology are discussed. By analogy with other cerebral arteriopathies, the aim of our management was to keep mean arterial blood pressure and end-tidal carbon dioxide so as to prevent any cerebral ischaemic or vasospastic phenomenon. We preserved the cerebral venous return by avoiding excessive head-down position. We used a balanced anaesthetic technique because it allows easier titration of the depth of anaesthesia with regard to mean arterial pressure. There is no contraindication to the use of loco-regional anaesthesia.

Br J Anaesth 2003; 91: 442–4

Keywords: anaesthesia; brain, cerebral auto-regulation; brain, cerebral ischaemia; complications, CADASIL syndrome


    Introduction
 Top
 Abstract
 Introduction
 Case description
 Discussion
 References
 
We describe the anaesthetic management of a 30-yr-old patient who needed urgent laparoscopy for torsion of a Fallopian tube. This patient also suffered from an ischaemic arteriopathy of the CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) type. The anaesthetic implications of this pathology are discussed. This disorder is rare and its precise incidence is currently unknown.


    Case description
 Top
 Abstract
 Introduction
 Case description
 Discussion
 References
 
A 30-yr-old woman presented for urgent laparoscopy with suspected torsion of a Fallopian tube. Her medical history included the following: (i) total thyroidectomy for the treatment of Graves disease, complicated by severe symptomatic post-operative hypoparathyroidism, which triggered one episode of seizures; (ii) benign ventricular extrasystole; and (iii) CADASIL disease, diagnosed after childbirth when she was 28 yr old. As a consequence of post-partum haemorrhage, systemic hypotension and fainting were followed by confusion and drowsiness for several hours. When the drowsiness had diminished, complete amnesia of the event and throbbing hemicranial headache accompanied by nausea and vomiting were observed. Since then, the headache had persisted almost uninterruptedly. Moreover, disabling photophobia and acouphobia set in progressively.

The clinical and neurological examination, carried out in the emergency room, was normal. The preoperative blood examination yielded normal results. The following medications were taken at home: thyroxine 200 µg, aspirin 160 mg, rocaltrol and calcium carbonate 8 g.

After premedication with ranitidine 50 mg and metoclopramide 10 mg i.v., the patient was taken to the operating theatre. With standard monitoring (ECG, pulse oximetry, non-invasive blood pressure, gas analyser and capnography) and pre-oxygenation, a rapid sequence induction with cricoid pressure using propofol, sufentanil and succinylcholine was carried out. Neuromuscular block was achieved with atracurium and controlled with train-of-four monitoring (Tof-Watch®; Organon International IWC, NJ, USA). Anaesthesia was maintained by controlled ventilation with an oxygen/air/desflurane mixture and the lungs were mechanically ventilated. After insufflation of the pneumoperitoneum, the patient was placed in a 30° head-down position.

Because it was an emergency case and no information or recommendations concerning the anaesthetic management of patients with CADASIL arteriopathy were available in textbooks or on the internet, we decided to keep mean arterial blood pressure greater than 60 mm Hg (=8 kPa) and end-tidal carbon dioxide around 40 mm Hg (=5.3 kPa) so as to prevent any cerebral ischaemic or vasospastic phenomena. Moreover, the cerebral venous return was preserved by restricting the head-down position to the minimum needed for the surgery and the head was kept in a neutral position. Surgery and recovery were uneventful. The neurological examination in the recovery room and later in the ward was normal.


    Discussion
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 Abstract
 Introduction
 Case description
 Discussion
 References
 
The CADASIL syndrome15 is an inherited neurological condition caused by non-atherosclerotic and non-amyloidosic micro-angiopathy. Linkage has been demonstrated with chromosome 19p13.1. At the molecular level, strongly stereotyped mutations in repetitive EGF-like domains in the extra-cellular portion of the trans-membrane notch-3 protein are observed. All these mutations result in the loss or gain of a cysteine residue, which suggests that the disease could result from abnormal disulphide bridge formation in the secondary or tertiary structure of the proteins. It is interesting that the locus of the NOTCH-3 gene is near that of the CACNL1A4 calcium channel gene, which carries the causal mutation of familial hemiplegic migraine and type II familial episodic ataxia. On the basis of the efficacy of acetazolamide (inhibitor of carbonic anhydrase) in channelopathies such as episodic ataxia, this treatment has been tried with some success in the prevention of migraine attacks in patients suffering from CADASIL.

At the histological level, the characteristic that is considered specific for CADASIL-type arteriopathy is the presence, on electronic microscopy, of dense osmophilic granular material in contact with the smooth muscular cells of the arterioles. This material is observed in brain tissue, in nerves and also in the dermis:6 7 this is why a skin biopsy is recommended to confirm the diagnosis of CADASIL. Moreover, in addition to establishing the diagnosis in the patient, skin biopsy also allows the screening of asymptomatic relatives.

From a clinical point of view, this disease has a natural history of recurrent ischaemic episodes affecting the white substance (71%). The signs and symptoms of the disease are: (i) migraine, with or without accompanying neurological signs (38%); (ii) cognitive problems (48%); (iii) epileptic attacks (10%); (iv) psychiatric symptoms (30%); and (v) dementia (28%), which is frequently accompanied by walking difficulties, urinary incontinence and pseudo-bulbar syndrome.

So far no treatment8 9 has proved to be efficient in influencing the natural evolution of this disease. From a purely empirical point of view, an anti-aggregant treatment may be proposed, on the basis that it may have a prophylactic effect on ischaemic attacks. It is essential to keep in mind that cerebral arteriography is highly inadvisable, for it is likely to induce vasospasm. Obviously, no fibrinolytic therapy should be attempted in the case of acute neurological deficit. The hormonal and cardiovascular changes related to pregnancy do not seem to influence CADASIL disease but, to our knowledge, this issue has not yet been described.

From the anaesthetic point of view, the frequent use of acetazolamide in these patients requires the preoperative measurement of blood electrolytes. In the case of general anaesthesia in patients with a cerebrovascular disease, it is important: (i) to keep the mean arterial blood pressure within the limits of cerebral autoregulation (as these limits are unknown in CADASIL disease, we used the limits used in non-hypertensive patients because the patient was not hypertensive); and (ii) to maintain normocapnia, to avoid both hyper- and hypocapnia, although the cerebral reactivity to carbon dioxide seems to be reduced in CADASIL disease.10

In our patient, we used balanced inhalation anaesthesia instead of an i.v. technique because the consequences of the cerebral vasoconstriction due to propofol are unknown in CADASIL disease. Moreover, the use of balanced anaesthesia allows easier titration of the depth of anaesthesia with regard to mean arterial pressure. Although cerebral autoregulation is better preserved with low-dose sevoflurane in patients with cerebrovascular disease,11 we did not use sevoflurane because neither EEG nor bispectral monitoring was available to diagnose any subclinical seizure-like activity, which may occur with high concentrations of sevoflurane.12 Isoflurane would have been the ideal choice but it was not available in the emergency room, and we therefore used desflurane.

Systemic blood pressure is best maintained by avoiding hypovolaemia. Should vasocontrictors be necessary, no experimental or clinical data are available and it is probably better to use direct vasoconstrictors (such as norepinephrine and neosinephrine) instead of indirect vasoconstrictors. In case of hypertensive problems, one should administer vasodilators such as sodium nitroprusside or nimodipine: by analogy to cerebral vasospasm, nimodipine is probably the first choice. Obstructions to the cerebral venous return and the head-down position should be avoided as much as possible. There is no contraindication to the use of loco-regional anaesthesia. Peripheral nerve blocks do not constitute a problem, but if central nerve blocks are used it is important to keep the mean arterial blood pressure within the limits of cerebral autoregulation and the usual precautions should be taken if the patient is on anti-aggregant therapy. Regarding postoperative analgesia, paracetamol, non-steroidal anti-inflammatory drugs can be used. Tramadol,13 given at a dose of 1 mg kg–1 i.v. over 10 min to prevent vomiting, has no effect on intracranial pressure and cerebral perfusion pressure and can be used to provide postoperative analgesia.

In conclusion, we describe the anaesthetic management of a young patient with CADASIL syndrome undergoing emergency laparoscopy. Many aspects of cerebral autoregulation in patients with this non-atherosclerotic cerebrovascular pathology are still unknown. By analogy with other cerebral arteriopathies, we propose maintaining normocapnia and keeping mean arterial pressure within the limits of normal cerebral autoregulation.


    References
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 Abstract
 Introduction
 Case description
 Discussion
 References
 
1 Blanco Menendez R, Aguado Balsas AM, Blanco E, et al. The cadasil syndrome: a model of sub-cortical disconnection. Rev Neurol 2001; 32: 750–4[ISI][Medline]

2 Hassan A, Markus HS. Genetics and ischaemic stroke. Brain 2000; 123: 1784–812[Abstract/Free Full Text]

3 Ito D, Tanahashi N, Murata M, et al. Notch 3 gene polymorphism and ischaemic cerebrovascular disease. J Neurol Neurosurg Psychiatry 2002; 72: 382–4[Abstract/Free Full Text]

4 Joutel A, Tournier-Lasserve E. Molecular basis and physiopathogenic mechanisms of CADASIL: a model of small vessel diseases of the brain. J Soc Biol 2002; 196: 109–15[Medline]

5 Kalimo H, Ruchoux MM, Viitanen, et al. CADASIL: a common form of hereditary arteriopathy causing brain infarcts and dementia. Brain Pathol 2002; 12: 371–84[ISI][Medline]

6 Rumbaugh JA, LaDuca JR, Shan Y, et al. CADASIL: the dermatologic diagnosis of a neurologic disease. J Am Acad Dermatol 2000; 43: 1128–30[CrossRef][ISI][Medline]

7 Wang T, Sharma SD, Fox N, et al. Description of a simple test for CADASIL disease and determination of mutation frequencies in sporadic ischaemic and dementia patients. J Neurol Neurosurg Psychiatry 2000; 69: 652–4[Abstract/Free Full Text]

8 Bounameaux H, Wutschert R. Drug treatment strategies for peripheral obliterative arteriopathy. Drugs 1998; 56 (Suppl. 3): 17–23[CrossRef][ISI][Medline]

9 Roman GC. Vascular dementia revisited: diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am 2002; 86: 477–99[ISI][Medline]

10 Pfefferkorn T, von Stuckrad-Barre S, Herzog J, et al. Reduced cerebrovascular CO2 reactivity in CADASIL: a transcranial Doppler sonography study. Stroke 2001; 32: 17–21[Abstract/Free Full Text]

11 Katsuyasu K, Hisatoshi O, Masakasu K, et al. Effects of sevoflurane on cerebral circulation and metabolism in patients with ischemic cerebrovascular disease. Anesthesiology 1993; 79: 704–9[ISI][Medline]

12 Hisao K, Satoshi T, Syoiti E, et al. Electrical seizures during sevoflurane anesthesia in two pediatric patients with epilepsy. Anesthesiology 1994; 81: 1535–7[ISI][Medline]

13 Ferber J, Juniewicz H, Glogowska E, et al. Tramadol for postoperative analgesia in intracranial surgery. Its effect on ICP and CPP. Neurol Neurochir Pol 2000; 34 (Suppl. 6): 70–9[Medline]





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