Ignoring The Evidence

Diagnosis of his wife's progressive multiple sclerosis would not have taken so long had doctors taken a proper history, says Dr David Wheldon

This is a personal story but I'm telling it because it illustrates much of what is wrong with medicine today.

Lessons of the past - such as the necessity for intuitive cross-disciplinary history taking - have been forgotten. And the intelligence of the individual practitioner has been steamrollered by the notion of 'evidence-based medicine'. This Orwellian phrase means nothing more or less than conformity with currently accepted practice.

In 1993, I married Sarah, an accomplished painter and violin restorer and dealer. One of our joys was walking in the countryside, often for long distances.

In 2000, on a walking holiday in the Auvergne, Sarah noticed that she was dragging her right foot a little. Once back home, she saw her GP, who sent her to an orthopaedic surgeon. He confidently made a diagnosis of congenital spinal stenosis. However, her condition deteriorated.

In 2003, her GP referred her to a neurologist. In the months between the ordering of the MRI and the scan itself, her deterioration accelerated. She became unable to walk unaided, and her right arm progressively weakened until she was unable to paint or to write. She was numb from the waist down. She had slurred speech, difficulty thinking and was often tired.

The scan revealed numerous white-matter hyperintensities. In a ten minute neurological consultation, she was given the diagnosis of progressive multiple sclerosis (MS). No treatment was available. She was simply advised to allow the disease to evolve.

Previous episodes
Let us hold the story there. The GP and the orthopaedic surgeon should have taken a history. In the past, Sarah had had two transient episodes of weakness of the right arm and one of dimmed vision in the right eye. Central neurological events separated in time and site raise immediate suspicions of MS. Sarah's disease might have been caught before it became progressive.

My Internet search back in 2003, found preliminary evidence that chronic disseminated infection with Chlamydia pneumoniae, a primary respiratory pathogen might be at the root of some variants of MS. C. pneumoniae gene-sequences had been found in the cerebrospinal fluid of a number of MS patients by workers at Vanderbilt University in the US.

There, patients treated for the infection - particularly those with early disease - had done well. Looking at Sarah's history, infection with C. pneumoniae seemed possible; the aggressive phase of her MS had been preceded by a mild but lengthy respiratory infection which had never resolved, instead tailing off into new-onset asthma. This is typical of C pneumoniae.

I didn't accept the current idea that progressive MS is untreatable and should be 'allowed to evolve'. So, after carrying out a quick risk/benefit analysis, I gave Sarah two antichlamydial agents: doxycycline plus roxithromycin. The latter is said to access the CNS, and has been used in treatment of neuroborreliosis.

What followed was dramatic. For a few days, Sarah had a Herxheimer-like reaction, with a fever and night sweats. After this, her mental fog and cognitive deficits speedily began to vanish. Slowly, the disease was rolled back - not the natural history of progressive MS, where spontaneous global recovery is rare .

After three months' treatment, Sarah was given pulses of oral metronidazole - there is evidence that protein synthesis inhibitors push the organism into an anaerobic state. The addition of metronidazole is cidal to the stalled organism, and extended Herxheimer-like reactions may be expected as bacterial endotoxin is released. This occurred.

Eventful recovery
Sarah's recovery was not uneventful. There was a host of phantom sensations as the numbness faded, and a brief episode of reflex sympathetic dystrophy of the right arm, presumably due to local inflammation following the death of intraneural bacteria. This was characterized by hyperhidrosis and hyperaem of the right arm, together with loss of function, and was accompanied by thalamic pain. At its most intense it lasted a week.

Now, 18 months later, Sarah is able to paint and to walk a mile or so. She received antibiotics continually for a year, and is now on intermittent treatment. Sequential MRI scans show shrinkage of the larger (and presumably the more recent and less gliotic) lesions.

Meanwhile, evidence has accrued, strengthening the link between MS and C. pneumoniae. At least five centres in different parts of the world have detected C. pneumoniae gene sequences in the cerebrospinal fluid of patients with MS; antibodies to the organisms are found there; new infection with C. pneumoniae heralds relapse; specific serology becomes statistically elevated as the disease becomes progressive; and the cerebrospinal fluid of patients with MS contains bacterial heat-shock proteins which cause oligodendrocyte precursors to undergo apoptosis.

There have also been two treatment studies. The first, a small, double-blind trial, showed shrinkage of brain lesion in relapsing-remitting disease with antichlamydial treatment. The second has shown a diminution in the number of MRI gadolinium-enhancing lesions in the brain during minocycline administration.

Evidence-based medicine is the hollowest of phrases. What evidence? Whose evidence? Thinking like this generates a Gadarine conformity of mental outlook which prevents scrutiny of the real evidence. Instead, potentially dangerous and usually unsuccessful treatments are used, at great cost.

The link between C. pneumoniae and MS is not yet proven, but the evidence is strong. It is heartbreaking to see patients with potentially treatable disease thrown onto the scrapheap because simple risk/benefit analyses are not made.

But, I, too, have to admit guilt. In my heart I had known for years that Sarah had MS, but I had not been able to face the implication of this diagnosis. Had I done so, Sarah would have received treatment earlier.

Before treatment, Sarah was slipping from grade 6 to grade 8 on the Kurtzke disability scale. Now she has returned to grade 2. She is still making improvements, particularly in her dexterity and stamina. Spasticity and clonus have gone. Given time, I feel we may be able to resume those long walks.
Hospital Doctor, 23rd June 2005

Dr Wheldon is a consultant medical microbiologist at Bedford Hospital

Vitamin Treatment Blocked MS Progression

New research from the US has raised hopes that vitamin therapy could be used to slow the progression of multiple sclerosis (MS), reports the BBC.

Scientists from the Children's Hospital Boston showed that when mice with MS symptoms were given a form of vitamin B3, called nicotinamide, nerve degeneration risk was reduced.

Crucially, the scientists found that daily nicotinamide shots protected the animals' nerve cells from myelin loss - myelin is fatty protein that ensures normal electrical impulses are passed to and from the brain. The vitamin shots also stabilised the condition of those cells that had already been affected. Furthermore, the researchers found that the greater the dose of nicotinamide, the greater the protective effect.

Now the US team wants to develop a trial for the therapy in human patients. Lead researcher Dr Shinjiro Kaneko said: "The earlier therapy was started, the better the effect, but we hope nicotinamide can help patients who are already in the later, chronic stage of MS."

Nicotinamide is one of the two principal forms of the B-complex vitamin niacin and is essential for growth and conversion of foods to energy. It has already been used in diabetes treatment and prevention.
Natural Products, 27th September 2006