Радиологическое представление Доусона о повторном переводе нескольких склерозов у молодой женщины: отчет о деле и обзор литературы.

Background

The prevalence of multiple sclerosis (MS) in the UK is 203.4 per 100,000 population in 2010, making MS the most common immune-mediated inflammatory demyelinating disease of central nervous system [ 1 , 2 ]. Pathologically MS is regarded as a multifocal area of demyelination associated with loss of oligodendrocytes, astroglial scarring, eventually resulting to axonal injury. This clinically translates into a spectrum of manifestations, ranging from typical forms of MS to many atypical manifestations.

Hence MS poses a diagnostic challenge, given the plausibility of differential diagnosis of many, varied, and rare disorders [ 3 ]. A single diagnostic test to unequivocally diagnose MS does not exist, and clinically we rely on a series of clinical, radiological, and laboratory findings to solidify the diagnosis. Magnetic resonance imaging (MRI) presents the gold-standard imaging modality for MS, with a sensitivity of 87% and specificity of 73% [ 4 ]. Nonetheless, a multitude of MRI findings associated with other disease states and incidental or false positive findings pose another diagnostic challenge [ 5 , 6 ].

A classification of MRI lesions suggestive of MS may present as ovoid or round entities, some are located around ventricles at a right angle from corpus callosum, giving as image of radiating from corpus callosum. These are described in literature as Dawson fingers, and they are best viewed on sagittal plane. Their diagnostic value resides in exclusion of MS-resembling diagnoses, such as MOG-antibody associated disease (MOGAD), which do not present with Dawson finger findings in MRI and lack specific oligoclonal G bands (Oligo-G) in cerebrospinal fluid (CSF) analysis [ 7 ]. Of note, Oligo-G bands are not a requirement for MS diagnosis but significantly increase clinical suspicion of MS in cases where MRI findings are not disseminated in space as per McDonald criteria. Nonetheless, in typical MS cases where McDonald criteria are met, cerebrospinal fluid (CSF) findings increase confidence in definitive MS diagnosis [ 8 ].

In this case report we explore the presentation of Dawson finger hyperintensities in the primary diagnostic MRI of a 26-year-old white Caucasian female with right sided dysesthesia as presenting complaint of relapsing remitting MS. Here we explore the sensitivity and specificity of Dawsons fingers upon MS diagnosis as well as their implications in differentiation between a family of demyelinating conditions with similar patient presentations.

Case presentation

A 26-year-old, female presented to the general practitioner with a 3-month history of altered sensation of the right side of body. The presenting symptom started in the lower leg with pins and needle sensation as well as hyperalgesia. There was a slow progression of symptoms in a distal to proximal direction. Of note, right leg symptoms subsided prior to right arm symptoms emerging. Dysesthesia also involved tongue and face. Solely the right side was affected, without any involvement of the left side, as reported by the patient. No obvious trigger was identified, and patient did not report any systemic symptoms at the time of presentation. Right sided symptoms resolved, and patient represented a month later with true vertigo, prompting further specialist and imaging follow up.

The clinical examination of her central nervous system revealed a right-handed lady who appears slightly anxious. Her visual acuity and fields are normal with no diplopia. Nystagmus and internuclear ophthalmoplegia (INO) associated findings were absent. Her pupils were equal, round, and reactive to light with accommodation. There was altered sensation involving the right half of body (face, hand, arm, leg, chest, and abdomen). Aside from the altered sensation in right sided facial, her cranial nerves were normal. Proprioception was normal. The assessment of her pyramidal function revealed normal tone, power (5/5), and reflexes in both upper and lower limbs. Plantars were downgoing. Cerebellar functions were normal. She had a normal tandem gait but swayed slightly on Romberg testing, which was quickly corrected. The patient did not have any significant past medical history and had a body mass index (BMI) of 20.44 kg/m 2 at presentation. Furthermore, she was not on any regular medications and reported no family history of note. She abstained from alcohol and had never smoked. She worked as a garage manager and as a beauty therapist. A referral was made for urgent neurological review and within a month the patient underwent a diagnostic MRI.

While waiting for further investigations under the national health system (NHS), the patient had an initial MRI, a month later from the onset of true vertigo, under a private, oversees neurologist suggestive of MS. The complete report however was not available to the authors. The patient had a further NHS-based, MRI scan 2 months following the onset of true vertigo. The latter identified bilateral periventricular T2 hyperintensities, strongly suggestive of demyelination plaques, with Dawson’s finger appearance around the trigone of the right lateral ventricle (Fig.  1 ). Further lesions were identified in the left side of the medulla and in the upper cervical cord. Taken collectively, both MRI scans identified strongly suggestive lesions of MS in two timepoints fulfilling the “dissemination in time and space (DIT and DIS)” parameters of the McDonald criteria (2017) [ 5 ]. To elaborate more on the MRI finding, the MRI reveals oval-shaped T2/FLAIR sequence hyperintense lesions in the white matter, commonly known as Dawson’s finger, indicative of demyelinating plaques. These lesions are predominantly located in the corpus callosum, potentially leading to cognitive dysfunction. Additionally, the corpus callosum might appear thinner.

Bilateral periventricular T2 hyperintensities strongly suggestive of demyelination plaques, with a quite typical Dawson’s finger appearance around the trigone of the right lateral ventricle (black arrows). There are also lesions in the left side of the medulla and in the upper cervical cord not visible in the sagittal view

Demyelinating plaques can also be found in other areas, such as deep white matter, around the ventricles, or in the infratentorial region, each associated with distinct symptoms. Moreover, there are small, round white matter lesions near the ventricles or in subcortical areas, which are generally non-specific and could be owing to microvascular ischemia. In patients with relapsing or progressive multiple sclerosis, subsequent imaging would likely reveal an increased number of white matter lesions.

Below is a table outlining potential sites for demyelinating lesions and their associated symptoms:

Corpus callosum

Infratentorial

Peri-ventricular

Further follow-up with blood test and lumbar puncture were arranged. Bloods were unremarkable with mildly elevated chloride (116 mEq/L) and Hb of 117 g per liter. Thyroid function tests were within normal parameters. Serum IgG, A, and M were within normal limits (Table  1 ). Patient was negative for Borrelia, syphilis, and human immunodeficiency virus (HIV) 1/2, and anti-myeloperoxidase and anti-proteinase 3 antibodies were negative. Lumbar puncture opening pressure was 15 mmHg, CFS culture was negative. Oligo-G bands were detected in the CFS.

Table 1 CSF and blood serum biochemical results CSF - Oligoclonal band: oligoclonal bands detected in CSF, with no corresponding bands in serum - CSF albumin 225 mg/L (normal range 0–350 mg/l) CSF IgG 49 mg/L (normal range 5–64 mg/l) Serum IgG 9 g/L (normal range 6–16 g/l) Serum IgA 1.4 g/L (normal range 0.8–2.8 g/l) Serum IgM 1.20 g/L (normal range 0.50–3 g/l) - CFS culture negative: negative for Borrelia, syphilis, and HIV Blood serum - ANA anti-myeloperoxidase: negative - Proteinase 3 normal - TFTs normal CSF Cerebrospinal fluid, HIV Human immunodeficiency virus

CSF and blood serum biochemical results

- Oligoclonal band: oligoclonal bands detected in CSF, with no corresponding bands in serum

- CSF albumin 225 mg/L (normal range 0–350 mg/l)

CSF IgG 49 mg/L (normal range 5–64 mg/l)

Serum IgG 9 g/L (normal range 6–16 g/l)

Serum IgA 1.4 g/L (normal range 0.8–2.8 g/l)

Serum IgM 1.20 g/L (normal range 0.50–3 g/l)

- CFS culture negative: negative for Borrelia, syphilis, and HIV

- ANA anti-myeloperoxidase: negative

- Proteinase 3 normal

- TFTs normal

CSF Cerebrospinal fluid, HIV Human immunodeficiency virus

The patient was formally diagnosed with relapsing remitting multiple sclerosis in June 2019, approximately 6 months post-initial presentation, following complete serological and imaging workup confirming the DIT and DIS character of the lesions identified, congruent with the patient’s symptomatology. The patient was treated with dimethyl fumarate initiated upon formal diagnosis with good response and no reported significant adverse events apart from occasional flushing.

Discussion

The Scottish pathologist James Walker Dawson (1870–1927) described “Dawson fingers” on histopathological specimens, for the first time, in his article in 1916. Nonetheless, the term “Dawson fingers” was coined by Charles Lumsden [ 9 ]. Pathological studies of patients with MS highlighting brain plaques surrounding and trailing medullary veins date back to 1983 [ 10 , 11 ]. Dawson fingers are not restricted to adult MS imaging manifestations and present a significant neuroradiological feature in the pediatric population [ 12 ].

Further studies have assessed MRI image markers that may differentiate between Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), MS, and aquaporin-4 (AQP4) antibody neuromyelitis optica (NMO) spectrum of diseases and found that Dawson’s fingers and jagged-border periventricular hyperintensities are a rare entity in NMO spectrum disorders but a common feature of MS [ 13 ]. More specifically, Dawson’s finger was present in 93% and 78% of patients with MS according to two author assessments, while present in only 5% and 0%, respectively, in patients with NMO MRI images [ 13 ]. Intriguingly, another manuscript highlighted Dawson finger sign in high incidence in patients with cerebral small vessel disease (CSVD) resulting from long-standing diabetes mellitus (DM) diagnosis [ 14 ]. This may raise the hypothesis that Dawson fingers are primarily venous integrity markers for exploring basic pathophysiology of CSVD. In the same study its worth mentioning that its more common to have Dawson’s finger in MS (69.65%) compared with patients with CSVD (30.8%). However, this distinction seems to reduce when comparing ratio of Dawson’s fingers in patients with MS (69%) versus CSVD who have DM (60%) [ 14 ]. In support of this statement, another manuscript, approaching the puzzling perivascular localization of demyelinating plaques by in silico analysis, suggested that over-expression of vascular endothelial growth factor (VEGF), as identified in the serum of patients with MS during active demyelination and chronic inactivated demyelinated lesions, may drive blood–brain barrier permeability and could promote MS relapse [ 15 , 16 ]. This finding could bridge the Dawson finger observations between the otherwise not associated disease entities, namely MS and CSVD. Vascular risk factors, such as hypertension, dyslipidaemia and diabetes, have been explored in the context of MS severity and shown to affect particular MS brain lesions differently. Smoking has been identified as unilaterally increasing the presence of Dawson fingers regardless of disease duration and consequently worsening prognosis. Other vascular risk factors did not present the same confounding results upon disease progression [ 17 ]. Consequently, smoking cessation may improve vascular outcomes and consequent neurological integrity in this patient group, presenting another link between vascular and neuronal interplay in MS. Furthermore, implementation of smoking cessation and mandatory VEGF serum testing, in this patient group may contribute to the management of MS, both from medical and cost–benefit analysis points of view [ 18 ].

In this case report, we aimed to present the intriguing imaging finding of “Dawson fingers” in a new MS diagnosis, highlight its historical but also contemporary use in definitive MS diagnosis in contrast to other neurodegenerative conditions and explore its manifestation as a junction marker of neurodemyelination and vascular integrity interplay in MS and CSVD maladies. The interaction between vascular and neuronal integrity in MS progression or even initiation warrants further research to untangle the effects of angiogenic factors, vascular compromise, and neuronal demyelination.

Conclusion

Dawson finger hyperintensities are important imaging findings in the primary diagnostic MRI for MS, they display high specificity for MS over all other demyelinating conditions.

Dawson finger hyperintensities are also seen in CSVD spectrum maladies. The interaction between vascular and neuronal integrity in MS progression warrants further research to understand vascular compromise and neuronal demyelination interplay.

Acknowledgements

The authors would like to thank Dr. E. Visser, Consultant Neurologist.

Abbreviations

Cerebral small vessel disease

Multiple sclerosis

MOG-antibody associated disease

Aquaporin-4

Dissemination in time

Dissemination in space

Author contributions

HA carried out literature review, manuscript writing, and approval of the final manuscript; SK carried out literature review, manuscript writing, revision of the manuscript, and approval of the final manuscript; OO approval of the final manuscript.

Funding

Not applicable.

Availability of data and materials

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.

Footnotes

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References

Associated Data

Data Availability Statement

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